Editing Helicobacter pylori

{{Short description|Species of bacteria}}
{{Featured article}}
{{cs1 config|name-list-style=vanc|display-authors = 6}}
{{Use dmy dates|date=August 2018}}
{{Speciesbox
| image = EMpylori.jpg
| image_caption = [[Electron micrograph]] of ''H. pylori'' possessing multiple [[flagella]] ([[negative staining]])
| genus = Helicobacter
| species = pylori
| authority = (Marshall ''et al.'' 1985) Goodwin ''et al.'', 1989
| synonyms =
* ''Campylobacter pylori'' <small>Marshall ''et al.'' 1985</small>
}}

'''''Helicobacter pylori''''', previously known as '''''Campylobacter pylori''''', is a [[gram-negative]], [[Flagellum#bacterial|flagellated]], [[Bacterial cellular morphologies#Helical|helical bacterium]]. Mutants can have a rod or curved rod shape that exhibits less [[virulence]].<ref name="Martínez">{{cite journal |vauthors=Martínez LE, O'Brien VP, Leverich CK, Knoblaugh SE, Salama NR |title=Nonhelical Helicobacter pylori Mutants Show Altered Gland Colonization and Elicit Less Gastric Pathology than Helical Bacteria during Chronic Infection |journal=Infect Immun |volume=87 |issue=7 |pages= |date=July 2019 |pmid=31061142 |pmc=6589060 |doi=10.1128/IAI.00904-18 |url=}}</ref><ref name="Salama">{{cite journal |vauthors=Salama NR |title=Cell morphology as a virulence determinant: lessons from Helicobacter pylori |journal=Curr Opin Microbiol |volume=54 |issue= |pages=11–17 |date=April 2020 |pmid=32014717 |pmc=7247928 |doi=10.1016/j.mib.2019.12.002 |url=}}</ref> Its [[Helix|helical]] body (from which the [[genus]] name ''[[Helicobacter]]'' derives) is thought to have evolved to penetrate the [[gastric mucosa|mucous lining]] of the [[stomach]], helped by its [[flagella]], and thereby establish infection.<ref name="Yamaoka">{{cite book |isbn=978-1-904455-31-8 |chapter-url=http://www.horizonpress.com/hpl2 |vauthors=Rust M, Schweinitzer T, Josenhans C |year=2008 |chapter=Helicobacter Flagella, Motility and Chemotaxis |title=''Helicobacter pylori'': Molecular Genetics and Cellular Biology |editor=Yamaoka, Y. |publisher=Caister Academic Press |access-date=1 April 2008 |archive-date=18 August 2016 |archive-url=https://web.archive.org/web/20160818123135/http://www.horizonpress.com/hpl2 |url-status=live }}</ref><ref name="Salama" /> While many earlier reports of an association between bacteria and the ulcers had existed, such as the works of [[John Lykoudis]],<ref>{{Cite journal |last=Kidd |first=Mark |last2=Modlin |first2=Irvin M. |date=1998 |title=A Century of Helicobacter pylori |url=https://karger.com/article/doi/10.1159/000007461 |journal=Digestion |language=en |volume=59 |issue=1 |pages=1–15 |doi=10.1159/000007461 |issn=0012-2823}}</ref><ref>{{Cite journal |last=Rigas |first=Basil |last2=Feretis |first2=Chris |last3=Papavassiliou |first3=Efstathios D |date=November 1999 |title=John Lykoudis: an unappreciated discoverer of the cause and treatment of peptic ulcer disease |url=https://linkinghub.elsevier.com/retrieve/pii/S0140673699060341 |journal=The Lancet |language=en |volume=354 |issue=9190 |pages=1634–1635 |doi=10.1016/S0140-6736(99)06034-1}}</ref><ref>{{Cite journal |last=Baird |first=A. Gordon |date=August 2016 |title=Is general practice in the wrong PLACE? |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC4979950/ |journal=The British Journal of General Practice: The Journal of the Royal College of General Practitioners |volume=66 |issue=649 |pages=424 |doi=10.3399/bjgp16X686329 |issn=1478-5242 |pmc=4979950 |pmid=27481970}}</ref><ref>{{Cite book |title=Helicobacter pioneers: firsthand accounts from the scientists who discovered helicobacters, 1892 - 1982 |date=2002 |publisher=Blackwell Science Asia |isbn=978-0-86793-035-1 |editor-last=Marshall |editor-first=Barry J. |edition=1. print |location=Carlton, South Victoria}}</ref> it was only in 1983 when the bacterium was formally described for the first time in the English-language Western literature as the causal agent of [[peptic ulcer|gastric ulcers]] by Australian [[physician-scientist]]s [[Barry Marshall]] and [[Robin Warren]].<ref>{{cite journal | vauthors = Warren JR, Marshall B | title = Unidentified curved bacilli on gastric epithelium in active chronic gastritis | journal = Lancet | volume = 1 | issue = 8336 | pages = 1273–5 | date = June 1983 | pmid = 6134060 | doi = 10.1016/S0140-6736(83)92719-8 | s2cid = 1641856 }}</ref><ref name="FitzGerald">{{cite book |vauthors=FitzGerald R, Smith SM |title=Helicobacter Pylori |chapter=An Overview of Helicobacter pylori Infection |series=Methods Mol Biol |volume=2283 |pages=1–14 |date=2021 |pmid=33765303 |doi=10.1007/978-1-0716-1302-3_1 |isbn=978-1-0716-1301-6 |s2cid=232365068 |chapter-url=}}</ref> In 2005, the pair was awarded the [[Nobel Prize in Physiology or Medicine]] for their discovery.<ref>{{cite journal |vauthors=Watts G |title=Nobel prize is awarded to doctors who discovered H pylori |journal=BMJ |volume=331 |issue=7520 |pages=795 |date=October 2005 |pmid=16210262 |pmc=1246068 |doi=10.1136/bmj.331.7520.795 |url=}}</ref>

Infection of the stomach with ''H. pylori'' does not necessarily cause illness: over half of the global population is infected, but most individuals are asymptomatic.<ref name="cancer.gov2023">{{cite web |title=Helicobacter pylori (H. pylori) and Cancer - NCI |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet |website=www.cancer.gov |access-date=18 October 2023 |language=en |date=25 September 2013 |archive-date=19 October 2023 |archive-url=https://web.archive.org/web/20231019062643/https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet |url-status=live }}</ref><ref name="de Brito">{{cite journal |vauthors=de Brito BB, da Silva FA, Soares AS, Pereira VA, Santos ML, Sampaio MM, Neves PH, de Melo FF |title=Pathogenesis and clinical management of Helicobacter pylori gastric infection |journal=World J Gastroenterol |volume=25 |issue=37 |pages=5578–5589 |date=October 2019 |pmid=31602159 |pmc=6785516 |doi=10.3748/wjg.v25.i37.5578 |doi-access=free }}</ref> Persistent [[colonisation (biology)|colonization]] with more virulent strains can induce a number of gastric and non-gastric disorders.<ref name="Chen">{{cite journal |vauthors=Chen CC, Liou JM, Lee YC, Hong TC, El-Omar EM, Wu MS |title=The interplay between Helicobacter pylori and gastrointestinal microbiota |journal=Gut Microbes |volume=13 |issue=1 |pages=1–22 |date=2021 |pmid=33938378 |pmc=8096336 |doi=10.1080/19490976.2021.1909459 |url=}}</ref> Gastric disorders due to infection begin with [[gastritis]], or inflammation of the stomach lining.<ref name="Matsuo">{{cite journal |vauthors=Matsuo Y, Kido Y, Yamaoka Y |title=Helicobacter pylori Outer Membrane Protein-Related Pathogenesis |journal=Toxins |volume=9 |issue=3 |date=March 2017 |page=101 |pmid=28287480 |pmc=5371856 |doi=10.3390/toxins9030101 |doi-access=free }}</ref> When infection is persistent, the prolonged inflammation will become [[chronic gastritis]]. Initially, this will be non-atrophic gastritis, but the damage caused to the stomach lining can bring about the development of [[atrophic gastritis]] and ulcers within the stomach itself or the [[duodenum]] (the nearest part of the intestine).<ref name="Matsuo"/> At this stage, the risk of developing [[gastric cancer]] is high.<ref name="Marghalani"/> However, the development of a [[duodenal ulcer]] confers a comparatively lower risk of cancer.<ref name="Koga">{{cite journal |vauthors=Koga Y |title=Microbiota in the stomach and application of probiotics to gastroduodenal diseases |journal=World J Gastroenterol |volume=28 |issue=47 |pages=6702–6715 |date=December 2022 |pmid=36620346 |pmc=9813937 |doi=10.3748/wjg.v28.i47.6702 |doi-access=free }}</ref> ''Helicobacter pylori'' are [[Carcinogenic bacteria|class 1 carcinogenic bacteria]], and potential cancers include gastric [[MALT lymphoma]] and [[gastric cancer]].<ref name="Matsuo"/><ref name="Marghalani">{{cite journal |vauthors=Marghalani AM, Bin Salman TO, Faqeeh FJ, Asiri MK, Kabel AM |title=Gastric carcinoma: Insights into risk factors, methods of diagnosis, possible lines of management, and the role of primary care |journal=J Family Med Prim Care |volume=9 |issue=6 |pages=2659–2663 |date=June 2020 |pmid=32984103 |pmc=7491774 |doi=10.4103/jfmpc.jfmpc_527_20 |doi-access=free }}</ref> Infection with ''H. pylori'' is responsible for an estimated 89% of all gastric cancers and is linked to the development of 5.5% of all cases cancers worldwide.<ref name="Shin">{{cite journal |vauthors=Shin WS, Xie F, Chen B, Yu J, Lo KW, Tse GM, To KF, Kang W |title=Exploring the Microbiome in Gastric Cancer: Assessing Potential Implications and Contextualizing Microorganisms beyond H. pylori and Epstein-Barr Virus |journal=Cancers |volume=15 |issue=20 |date=October 2023 |page=4993 |pmid=37894360 |pmc=10605912 |doi=10.3390/cancers15204993 |doi-access=free }}</ref><ref name="Violeta">{{cite journal | vauthors = Violeta Filip P, Cuciureanu D, Sorina Diaconu L, Maria Vladareanu A, Silvia Pop C | title = MALT lymphoma: epidemiology, clinical diagnosis and treatment | journal = Journal of Medicine and Life | volume = 11 | issue = 3 | pages = 187–193 | date = 2018 | pmid = 30364585 | pmc = 6197515 | doi = 10.25122/jml-2018-0035 }}</ref> ''H. pylori'' is the only bacterium known to cause cancer.<ref name="Ruggiero">{{cite journal |vauthors=Ruggiero P |title=Use of probiotics in the fight against Helicobacter pylori |journal=World J Gastrointest Pathophysiol |volume=5 |issue=4 |pages=384–91 |date=November 2014 |pmid=25400981 |pmc=4231502 |doi=10.4291/wjgp.v5.i4.384 |doi-access=free }}</ref>

Extragastric complications that have been linked to ''H. pylori'' include [[anemia]] due either to iron deficiency or [[vitamin B12 deficiency]], [[Diabetes|diabetes mellitus]], cardiovascular illness, and certain neurological disorders.<ref name="WJG2020">{{cite journal |vauthors=Santos ML, de Brito BB, da Silva FA, Sampaio MM, Marques HS, Oliveira E, Silva N, de Magalhães Queiroz DM, de Melo FF |title=Helicobacter pylori infection: Beyond gastric manifestations |journal=World J Gastroenterol |volume=26 |issue=28 |pages=4076–4093 |date=July 2020 |pmid=32821071 |pmc=7403793 |doi=10.3748/wjg.v26.i28.4076 |doi-access=free |url=}}</ref> An inverse association has also been claimed with ''H. pylori'' having a positive protective effect against [[asthma]], [[esophageal cancer]], [[inflammatory bowel disease]] (including [[gastroesophageal reflux disease]] and [[Crohn's disease]]), and others.<ref name="WJG2020"/>

Some studies suggest that ''H. pylori'' plays an important role in the natural stomach ecology by influencing the type of bacteria that colonize the gastrointestinal tract.<ref name="Blaser 2006"/><ref name="Gravina">{{cite journal|vauthors=Gravina AG, Zagari RM, De Musis C, Romano L, Loguercio C, Romano M|date=August 2018|title=Helicobacter pylori and extragastric diseases: A review|journal=World Journal of Gastroenterology|type=Review|volume=24|issue=29|pages=3204–3221|doi=10.3748/wjg.v24.i29.3204|pmc=6079286|pmid=30090002 |doi-access=free }}</ref> Other studies suggest that non-pathogenic strains of ''H. pylori'' may beneficially normalize stomach acid secretion, and regulate appetite.<ref name="AckermanScientificAmerican">{{cite magazine | vauthors = Ackerman J | title = The ultimate social network | volume = 306 | issue = 6 | pages = 36–43 | date = June 2012 | pmid = 22649992 | doi = 10.1038/scientificamerican0612-36 | magazine = Scientific American }}</ref>

In 2023, it was estimated that about two-thirds of the world's population was infected with ''H. pylori'', being more common in [[developing countries]].<ref name="CDC2024">{{cite web |title=Helicobacter pylori {{!}} CDC Yellow Book 2024 |url=https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/helicobacter-pylori |website=wwwnc.cdc.gov |access-date=20 October 2023 |archive-date=22 October 2023 |archive-url=https://web.archive.org/web/20231022070847/https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/helicobacter-pylori |url-status=live }}</ref> The prevalence has declined in many countries due to [[Helicobacter pylori eradication protocols|eradication treatments]] with antibiotics and [[proton-pump inhibitor]]s, and with increased [[standards of living]].<ref name=Li2023/><ref name=HooiLai2017>{{cite journal | vauthors = Hooi JK, Lai WY, Ng WK, Suen MM, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VW, Wu JC, Chan FK, Sung JJ, Kaplan GG, Ng SC | title = Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis | journal = Gastroenterology | volume = 153 | issue = 2 | pages = 420–429 | date = August 2017 | pmid = 28456631 | doi = 10.1053/j.gastro.2017.04.022 | doi-access = free }}</ref>
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==Microbiology==
''Helicobacter pylori'' is a species of [[gram-negative bacteria]] in the ''[[Helicobacter]]'' genus.<ref>{{cite journal |vauthors=Goodwin CS, Armstrong JA, Chilvers T, etal |title = Transfer of ''Campylobacter pylori'' and ''Campylobacter mustelae'' to ''Helicobacter'' gen. nov. as ''Helicobacter pylori'' comb. nov. and ''Helicobacter mustelae'' comb. nov., respectively|journal = Int. J. Syst. Bacteriol.|year = 1989 |volume = 39 |issue = 4 |pages = 397–405 |doi = 10.1099/00207713-39-4-397|doi-access = free}}</ref>
About half the world's population is infected with ''H. pylori'' but only a few strains are [[pathogenic]]. ''H pylori'' is a [[helical bacterium]] having a predominantly [[Helix|helical shape]], also often described as having a spiral or ''S'' shape.<ref name="Martínez2">{{cite journal |vauthors=Martínez LE, Hardcastle JM, Wang J, Pincus Z, Tsang J, Hoover TR, Bansil R, Salama NR |title=Helicobacter pylori strains vary cell shape and flagellum number to maintain robust motility in viscous environments |journal=Mol Microbiol |volume=99 |issue=1 |pages=88–110 |date=January 2016 |pmid=26365708 |pmc=4857613 |doi=10.1111/mmi.13218 |url=}}</ref><ref name="O'Rourke2">{{cite book |last1=O'Rourke |first1=Jani |last2=Bode |first2=Günter |title=Morphology and Ultrastructure |url=https://www.ncbi.nlm.nih.gov/books/NBK2452/ |publisher=ASM Press |date=2001|pmid=21290748 |isbn=978-1-55581-213-3 }}</ref> Its helical shape is better suited for progressing through the viscous [[gastric mucosa|mucosa lining of the stomach]], and is maintained by a number of [[protease|enzymes]] in the [[bacterial cell wall|cell wall's]] [[peptidoglycan]].<ref name="Martínez"/> The bacteria reach the less acidic mucosa by use of their [[Flagellum|flagella]].<ref name="Kao">{{cite journal |vauthors=Kao CY, Sheu BS, Wu JJ |title=Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis |journal=Biomedical Journal |volume=39 |issue=1 |pages=14–23 |date=February 2016 |pmid=27105595 |pmc=6138426 |doi=10.1016/j.bj.2015.06.002 |url=}}</ref> Three strains studied showed a variation in length from 2.8 to 3.3&nbsp;μm but a fairly constant diameter of 0.55–0.58&nbsp;[[micrometre|μm]].<ref name="Martínez2" /> ''H. pylori'' can convert from a helical to an inactive [[coccus|coccoid]] form that can evade the immune system, and that may possibly become viable, known as [[viable but nonculturable]] (VBNC).<ref name="Ieradi">{{cite journal |vauthors=Ierardi E, Losurdo G, Mileti A, Paolillo R, Giorgio F, Principi M, Di Leo A |title=The Puzzle of Coccoid Forms of Helicobacter pylori: Beyond Basic Science |journal=Antibiotics |volume=9 |issue=6 |date=May 2020 |page=293 |pmid=32486473 |pmc=7345126 |doi=10.3390/antibiotics9060293 |doi-access=free |url=}}</ref><ref name="Luo">{{cite journal |vauthors=Luo Q, Liu N, Pu S, Zhuang Z, Gong H, Zhang D |title=A review on the research progress on non-pharmacological therapy of Helicobacter pylori |journal=Front Microbiol |volume=14 |issue= |pages=1134254 |date=2023 |pmid=37007498 |pmc=10063898 |doi=10.3389/fmicb.2023.1134254 |doi-access=free |url=}}</ref>

''Helicobacter pylori'' is [[microaerophilic]] – that is, it requires [[oxygen]], but at lower concentration than in the [[earth's atmosphere|atmosphere]]. It contains a [[hydrogenase]] that can produce energy by oxidizing molecular [[hydrogen]] (H<sub>2</sub>) made by [[Gut microbiota|intestinal bacteria]].<ref>{{cite journal | vauthors = Olson JW, Maier RJ | title = Molecular hydrogen as an energy source for Helicobacter pylori | journal = Science | volume = 298 | issue = 5599 | pages = 1788–90 | date = November 2002 | pmid = 12459589 | doi = 10.1126/science.1077123 | s2cid = 27205768 | bibcode = 2002Sci...298.1788O }}</ref>

''H.&nbsp;pylori'' can be demonstrated in tissue by [[Gram stain]], [[Giemsa stain]], [[H&E stain]], [[Warthin–Starry stain|Warthin-Starry silver stain]], [[Acridine orange|acridine orange stain]], and [[phase-contrast microscopy]]. It is capable of forming [[biofilm]]s. Biofilms help to hinder the action of antibiotics and can contribute to treatment failure.<ref name="Baj">{{cite journal |vauthors=Baj J, Forma A, Sitarz M, Portincasa P, Garruti G, Krasowska D, Maciejewski R |title=Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment |journal=Cells |volume=10 |issue=1 |date=December 2020 |page=27 |pmid=33375694 |pmc=7824444 |doi=10.3390/cells10010027 |doi-access=free |url=}}</ref><ref name="Elshenawi2023">{{cite journal |vauthors=Elshenawi Y, Hu S, Hathroubi S |title=Biofilm of Helicobacter pylori: Life Cycle, Features, and Treatment Options |journal=Antibiotics |volume=12 |issue=8 |date=July 2023 |page=1260 |pmid=37627679 |pmc=10451559 |doi=10.3390/antibiotics12081260 |doi-access=free }}</ref>

To successfully colonize its host, ''H. pylori'' uses many different [[virulence factor]]s including [[oxidase]], [[catalase]], and [[urease]].<ref name="Kusters2006">{{cite journal | vauthors = Kusters JG, van Vliet AH, Kuipers EJ | title = Pathogenesis of Helicobacter pylori infection | journal = Clinical Microbiology Reviews | volume = 19 | issue = 3 | pages = 449–90 | date = July 2006 | pmid = 16847081 | pmc = 1539101 | doi = 10.1128/CMR.00054-05 }}</ref> Urease is the most abundant protein, its expression representing about 10% of the total protein weight.<ref name="Alzahrani">{{cite journal |vauthors=Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE |title=Effect of Helicobacter pylori on gastric epithelial cells |journal=World J Gastroenterol |volume=20 |issue=36 |pages=12767–80 |date=September 2014 |pmid=25278677 |pmc=4177462 |doi=10.3748/wjg.v20.i36.12767 |doi-access=free |url=}}</ref>

''H.&nbsp;pylori'' possesses five major [[outer membrane protein]] families.<ref name="Kusters2006"/> The largest family includes known and putative [[Bacterial adhesin|adhesins]]. The other four families are [[Porin (protein)|porin]]s, iron transporters, [[flagella|flagellum]]-associated proteins, and proteins of unknown function. Like other typical gram-negative bacteria, the outer membrane of ''H.&nbsp;pylori'' consists of [[phospholipids]] and [[lipopolysaccharide]] (LPS). The [[Lipopolysaccharide#O-antigen|O-antigen]] of LPS may be [[fucose|fucosylated]] and mimic [[Lewis antigen system|Lewis blood group antigens]] found on the gastric epithelium.<ref name="Kusters2006"/>

===Genome===
''Helicobacter pylori'' consists of a large diversity of strains, and hundreds of [[genome]]s have been completely [[sequencing|sequenced]].<ref>{{cite web |url=http://genolist.pasteur.fr/PyloriGene |title=Genome information for the ''H.&nbsp;pylori'' 26695 and J99 strains |publisher=Institut Pasteur |year=2002 |access-date=1 September 2008 |archive-date=26 November 2017 |archive-url=https://web.archive.org/web/20171126221437/http://genolist.pasteur.fr/PyloriGene/ |url-status=live }}</ref><ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=139 |title=''Helicobacter pylori'' J99, complete genome |publisher=National Center for Biotechnology Information |access-date=1 September 2008 |archive-date=6 April 2011 |archive-url=https://web.archive.org/web/20110406134345/http://www.ncbi.nlm.nih.gov/sites/entrez?db=genome |url-status=live }}</ref><ref name="Oh">{{cite journal | vauthors = Oh JD, Kling-Bäckhed H, Giannakis M, Xu J, Fulton RS, Fulton LA, Cordum HS, Wang C, Elliott G, Edwards J, Mardis ER, Engstrand LG, Gordon JI | title = The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: evolution during disease progression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 26 | pages = 9999–10004 | date = June 2006 | pmid = 16788065 | pmc = 1480403 | doi = 10.1073/pnas.0603784103 | bibcode = 2006PNAS..103.9999O | doi-access = free }}</ref> The genome of the strain ''26695'' consists of about 1.7&nbsp;million [[base pair]]s, with some 1,576&nbsp;genes.<ref name="NCBI">{{cite web |title=Helicobacter pylori 26695 genome assembly ASM30779v1 |url=https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000307795.1/ |website=NCBI |access-date=4 June 2024 |language=en}}</ref><ref name="Tomb 1997">{{cite journal | vauthors = Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou L, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Hickey EK, Berg DE, Gocayne JD, Utterback TR, Peterson JD, Kelley JM, Cotton MD, Weidman JM, Fujii C, Bowman C, Watthey L, Wallin E, Hayes WS, Borodovsky M, Karp PD, Smith HO, Fraser CM, Venter JC | title = The complete genome sequence of the gastric pathogen Helicobacter pylori | journal = Nature | volume = 388 | issue = 6642 | pages = 539–47 | date = August 1997 | pmid = 9252185 | doi = 10.1038/41483 | s2cid = 4411220 | bibcode = 1997Natur.388..539T | doi-access = free }}</ref> The [[pan-genome]], that is the combined set of 30&nbsp;sequenced strains, encodes 2,239&nbsp;protein families ([[Sequence homology#Orthology|orthologous groups]] OGs).<ref>{{cite journal | vauthors = van Vliet AH | title = Use of pan-genome analysis for the identification of lineage-specific genes of Helicobacter pylori | journal = FEMS Microbiology Letters | volume = 364 | issue = 2 | pages = fnw296 | date = January 2017 | pmid = 28011701 | doi = 10.1093/femsle/fnw296 | doi-access = free }}</ref> Among them, 1,248&nbsp;OGs are conserved in all the 30&nbsp;strains, and represent the [[Pan-genome#Core|universal core]]. The remaining 991&nbsp;OGs correspond to the [[Pan-genome#Cloud|accessory genome]] in which 277&nbsp;OGs are unique to one strain.<ref>{{cite journal | vauthors = Uchiyama I, Albritton J, Fukuyo M, Kojima KK, Yahara K, Kobayashi I | title = A Novel Approach to Helicobacter pylori Pan-Genome Analysis for Identification of Genomic Islands | journal = PLOS ONE | volume = 11 | issue = 8 | pages = e0159419 | date = 9 August 2016 | pmid = 27504980 | pmc = 4978471 | doi = 10.1371/journal.pone.0159419 | bibcode = 2016PLoSO..1159419U | doi-access = free }}</ref>

There are eleven [[restriction modification system]]s in the genome of ''H. pylori''.<ref name="Tomb 1997" /> This is an unusually high number providing a [[DNA methylation#In bacteria|defence against bacteriophages]].<ref name="Tomb 1997" />

===Transcriptome===
[[Single-cell transcriptomics]] using [[Single-cell transcriptomics#Single-cell RNA-seq|single-cell RNA-Seq]] gave the complete [[transcriptome]] of ''H. pylori'' which was published in 2010. This analysis of its [[Bacterial transcription|transcription]] confirmed the known acid induction of major [[Virulence factor|virulence]] loci, including the urease (ure) operon and the Cag [[pathogenicity island]] (PAI).<ref name="Sharma2010">{{cite journal | vauthors = Sharma CM, Hoffmann S, Darfeuille F, Reignier J, Findeiss S, Sittka A, Chabas S, Reiche K, Hackermüller J, Reinhardt R, Stadler PF, Vogel J | title = The primary transcriptome of the major human pathogen Helicobacter pylori | journal = Nature | volume = 464 | issue = 7286 | pages = 250–5 | date = March 2010 | pmid = 20164839 | doi = 10.1038/nature08756 | bibcode = 2010Natur.464..250S | s2cid = 205219639 }}</ref> A total of 1,907&nbsp;[[transcription start site]]s 337&nbsp;primary [[operon]]s, and 126&nbsp;additional suboperons, and 66&nbsp;mono[[cistron]]s were identified. Until 2010, only about 55&nbsp;transcription start sites (TSSs) were known in this species. 27% of the primary TSSs are also antisense TSSs, indicating that – similar to ''[[Escherichia coli|E.&nbsp;coli]]'' – [[Antisense RNA|antisense transcription]] occurs across the entire ''H.&nbsp;pylori'' genome. At least one antisense TSS is associated with about 46% of all [[open reading frame]]s, including many [[housekeeping gene]]s.<ref name="Sharma2010"/> About 50% of the [[Five prime untranslated region|5{{prime}} UTRs]] (leader sequences) are 20–40&nbsp;nucleotides (nt) in length and support the AAGGag motif located about 6&nbsp;nt (median distance) upstream of start codons as the consensus [[Shine-Dalgarno sequence|Shine–Dalgarno sequence]] in ''H.&nbsp;pylori''.<ref name="Sharma2010"/>

=== Proteome ===
The [[proteome]] of ''H. pylori'' has been systematically analyzed and more than 70% of its [[protein]]s have been detected by [[mass spectrometry]], and other methods. About 50% of the proteome has been quantified, informing of the number of protein copies in a typical cell.<ref>{{cite journal|date=2015-08-03|title=Stable isotope labeling by amino acids in cell culture based proteomics reveals differences in protein abundances between spiral and coccoid forms of the gastric pathogen Helicobacter pylori|url=https://www.sciencedirect.com/science/article/abs/pii/S1874391915300099|journal=Journal of Proteomics|language=en|volume=126|pages=34–45|doi=10.1016/j.jprot.2015.05.011|issn=1874-3919|last1=Müller|first1=Stephan A.|last2=Pernitzsch|first2=Sandy R.|last3=Haange|first3=Sven-Bastiaan|last4=Uetz|first4=Peter|last5=von Bergen|first5=Martin|last6=Sharma|first6=Cynthia M.|last7=Kalkhof|first7=Stefan|pmid=25979772|s2cid=415255|access-date=26 July 2021|archive-date=27 July 2021|archive-url=https://web.archive.org/web/20210727071501/https://www.sciencedirect.com/science/article/abs/pii/S1874391915300099|url-status=live}}</ref>

Studies of the [[interactome]] have identified more than 3000 [[protein-protein interactions]]. This has provided information of how proteins interact with each other, either in stable [[protein complex]]es or in more dynamic, transient interactions, which can help to identify the functions of the protein. This in turn helps researchers to find out what the function of uncharacterized proteins is, e.g. when an uncharacterized protein interacts with several proteins of the [[ribosome]] (that is, it is likely also involved in ribosome function). About a third of all ~1,500 proteins in ''H. pylori'' remain uncharacterized and their function is largely unknown.<ref name="Wuchty">{{cite journal |vauthors=Wuchty S, Müller SA, Caufield JH, Häuser R, Aloy P, Kalkhof S, Uetz P |title=Proteome Data Improves Protein Function Prediction in the Interactome of Helicobacter pylori |journal=Mol Cell Proteomics |volume=17 |issue=5 |pages=961–973 |date=May 2018 |pmid=29414760 |pmc=5930399 |doi=10.1074/mcp.RA117.000474 |doi-access=free |url=}}</ref>

==Infection==
[[File:H pylori ulcer diagram en.png|thumb|upright=1.5| Diagram of stages of ulcer development]]
An infection with ''Helicobacter pylori'' can either have no symptoms even when lasting a lifetime, or can harm the stomach and duodenal [[Mucous membrane|linings]] by [[Inflammation|inflammatory responses]] induced by several mechanisms associated with a number of [[virulence factor]]s. [[Colonisation (biology)|Colonization]] can initially cause ''H. pylori induced gastritis'', an [[Gastritis|inflammation of the stomach lining]] that became a listed disease in [[ICD11]].<ref name="Maastricht 2022"/><ref name="ICD11"/><ref name="medscape2024" /> This will progress to [[chronic gastritis]] if left untreated. Chronic gastritis may lead to [[atrophic gastritis|atrophy]] of the stomach lining, and the development of [[peptic ulcer]]s (gastric or duodenal). These changes may be seen as stages in the development of [[gastric cancer]], known as ''Correa's cascade''.<ref name="Repetto">{{cite journal |vauthors=Repetto O, Vettori R, Steffan A, Cannizzaro R, De Re V |title=Circulating Proteins as Diagnostic Markers in Gastric Cancer |journal=Int J Mol Sci |volume=24 |issue=23 |date=November 2023 |page=16931 |pmid=38069253 |pmc=10706891 |doi=10.3390/ijms242316931 |doi-access=free |url=}}</ref><ref name="Livzan">{{cite journal |vauthors=Livzan MA, Mozgovoi SI, Gaus OV, Shimanskaya AG, Kononov AV |title=Histopathological Evaluation of Gastric Mucosal Atrophy for Predicting Gastric Cancer Risk: Problems and Solutions |journal=Diagnostics |volume=13 |issue=15 |date=July 2023 |page=2478 |pmid=37568841 |pmc=10417051 |doi=10.3390/diagnostics13152478 |doi-access=free |url=}}</ref> Extragastric complications that have been linked to ''H. pylori'' include [[anemia]] due either to iron-deficiency or vitamin B12 deficiency, diabetes mellitus, cardiovascular, and certain neurological disorders.<ref name="WJG2020" />

Peptic ulcers are a consequence of inflammation that allows stomach acid and the digestive enzyme [[pepsin]] to overwhelm the protective mechanisms of the [[mucous membranes]]. The location of colonization of ''H.&nbsp;pylori'', which affects the location of the ulcer, depends on the acidity of the stomach.<ref name="Dixon">{{cite journal | vauthors = Dixon MF | title = Patterns of inflammation linked to ulcer disease | journal = Baillière's Best Practice & Research. Clinical Gastroenterology | volume = 14 | issue = 1 | pages = 27–40 | date = February 2000 | pmid = 10749087 | doi = 10.1053/bega.1999.0057 }}</ref> In people producing large amounts of acid, ''H.&nbsp;pylori'' colonizes near the [[pyloric antrum]] (exit to the duodenum) to avoid the acid-secreting [[parietal cells]] at the [[fundus (stomach)|fundus]] (near the entrance to the stomach).<ref name="Kusters2006"/> [[G cell]]s express relatively high levels of [[PD-L1]] that protects these cells from ''H. pylori''-induced immune destruction.<ref>{{cite journal | vauthors = Mommersteeg MC, Yu BT, van den Bosch TP, von der Thüsen JH, Kuipers EJ, Doukas M, Spaander MC, Peppelenbosch MP, Fuhler GM | title = Constitutive programmed death ligand 1 expression protects gastric G-cells from Helicobacter pylori-induced inflammation | journal = Helicobacter | volume = 27 | issue = 5 | pages = e12917 | date = October 2022 | pmid = 35899973 | doi = 10.1111/hel.12917| pmc = 9542424 | s2cid = 251132578 }}</ref> In people producing normal or reduced amounts of acid, ''H.&nbsp;pylori'' can also colonize the rest of the stomach.

[[File:2414 Stomach.jpg|thumb|upright=0.8|Diagram showing parts of the stomach]]
The inflammatory response caused by bacteria colonizing near the pyloric antrum induces G cells in the antrum to secrete the hormone [[gastrin]], which travels through the bloodstream to parietal cells in the fundus.<ref name="pmid14755326">{{cite journal | vauthors = Blaser MJ, Atherton JC | title = Helicobacter pylori persistence: biology and disease | journal = The Journal of Clinical Investigation | volume = 113 | issue = 3 | pages = 321–33 | date = February 2004 | pmid = 14755326 | pmc = 324548 | doi = 10.1172/JCI20925 }}</ref> Gastrin stimulates the parietal cells to secrete more acid into the stomach lumen, and over time increases the number of parietal cells, as well.<ref name="Schubert 2008">{{cite journal | vauthors = Schubert ML, Peura DA | title = Control of gastric acid secretion in health and disease | journal = Gastroenterology | volume = 134 | issue = 7 | pages = 1842–60 | date = June 2008 | pmid = 18474247 | doi = 10.1053/j.gastro.2008.05.021 | s2cid = 206210451 }}</ref> The increased acid load damages the duodenum, which may eventually lead to the formation of ulcers.

''Helicobacter pylori'' is a class I [[carcinogen]], and potential cancers include gastric [[mucosa-associated lymphoid tissue]] (MALT) [[lymphoma]]s and [[gastric cancer]].<ref name="Matsuo"/><ref name="Marghalani"/><ref name="Abbas">{{cite journal | vauthors = Abbas H, Niazi M, Makker J | title = Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Colon: A Case Report and a Literature Review | journal = The American Journal of Case Reports | volume = 18 | pages = 491–497 | date = May 2017 | pmid = 28469125 | pmc = 5424574 | doi = 10.12659/AJCR.902843 }}</ref> Less commonly, [[diffuse large B-cell lymphoma]] of the stomach is a risk.<ref name="pmid25852262">{{cite journal | vauthors = Paydas S | title = Helicobacter pylori eradication in gastric diffuse large B cell lymphoma | journal = World Journal of Gastroenterology | volume = 21 | issue = 13 | pages = 3773–6 | date = April 2015 | pmid = 25852262 | pmc = 4385524 | doi = 10.3748/wjg.v21.i13.3773 | doi-access = free }}</ref> Infection with ''H. pylori'' is responsible for around 89 per cent of all gastric cancers, and is linked to the development of 5.5 per cent of all cases of cancer worldwide.<ref name="Shin"/><ref name="Violeta"/> Although the data varies between different countries, overall about 1% to 3% of people infected with ''Helicobacter pylori'' develop gastric cancer in their lifetime compared to 0.13% of individuals who have had no ''H.&nbsp;pylori'' infection.<ref>{{cite journal | vauthors = Kuipers EJ | title = Review article: exploring the link between Helicobacter pylori and gastric cancer | journal = Alimentary Pharmacology & Therapeutics | volume = 13 | pages = 3–11 | date = March 1999 | issue = Suppl 1 | pmid = 10209681 | doi = 10.1046/j.1365-2036.1999.00002.x | s2cid = 19231673 }}</ref><ref name="Kusters2006"/> ''H.&nbsp;pylori''-induced gastric cancer is the third highest cause of worldwide cancer mortality as of 2018.<ref name="Feral">{{cite journal | vauthors = Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F | title = Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods | journal = International Journal of Cancer | volume = 144 | issue = 8 | pages = 1941–1953 | date = April 2019 | pmid = 30350310 | doi = 10.1002/ijc.31937 | doi-access = free }}</ref> Because of the usual lack of symptoms, when gastric cancer is finally diagnosed it is often fairly advanced. More than half of gastric cancer patients have lymph node metastasis when they are initially diagnosed.<ref name="pmid24744586">{{cite journal | vauthors = Deng JY, Liang H | title = Clinical significance of lymph node metastasis in gastric cancer | journal = World Journal of Gastroenterology | volume = 20 | issue = 14 | pages = 3967–75 | date = April 2014 | pmid = 24744586 | pmc = 3983452 | doi = 10.3748/wjg.v20.i14.3967 | doi-access = free }}</ref>
[[File: Helicobacter pylori2.jpg|thumb|Micrograph of ''H. pylori'' colonizing the [[gastric mucosa|stomach lining]]]]
Chronic inflammation that is a feature of cancer development is characterized by infiltration of [[neutrophil]]s and [[macrophage]]s to the gastric epithelium, which favors the accumulation of [[inflammatory cytokine|pro-inflammatory cytokines]], [[reactive oxygen species]] (ROS) and [[reactive nitrogen species]] (RNS) that cause [[DNA damage]].<ref name=Valenzuela>{{cite journal | vauthors = Valenzuela MA, Canales J, Corvalán AH, Quest AF | title = Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis | journal = World Journal of Gastroenterology | volume = 21 | issue = 45 | pages = 12742–56 | date = December 2015 | pmid = 26668499 | pmc = 4671030 | doi = 10.3748/wjg.v21.i45.12742 | doi-access = free }}</ref> The [[DNA oxidation|oxidative DNA damage]] and levels of [[oxidative stress]] can be indicated by a biomarker, [[DNA oxidation#Increased 8-oxo-dG in carcinogenesis and disease|8-oxo-dG]].<ref name=Valenzuela/><ref name="Raza">{{cite journal | vauthors = Raza Y, Khan A, Farooqui A, Mubarak M, Facista A, Akhtar SS, Khan S, Kazi JI, Bernstein C, Kazmi SU | title = Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis | journal = Pathology & Oncology Research | volume = 20 | issue = 4 | pages = 839–46 | date = October 2014 | pmid = 24664859 | doi = 10.1007/s12253-014-9762-1 | s2cid = 18727504 }}</ref> Other damage to DNA includes [[double-strand break]]s.<ref name=Koeppel>{{cite journal | vauthors = Koeppel M, Garcia-Alcalde F, Glowinski F, Schlaermann P, Meyer TF | title = Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells | journal = Cell Reports | volume = 11 | issue = 11 | pages = 1703–13 | date = June 2015 | pmid = 26074077 | doi = 10.1016/j.celrep.2015.05.030 | doi-access = free }}</ref>

Small [[Gastric polyp|gastric]] and [[colorectal polyp]]s are [[adenoma]]s that are more commonly found in association with the mucosal damage induced by ''H. pylori'' gastritis.<ref name="Markowski"/><ref name="Dong">{{cite journal |vauthors=Dong YF, Guo T, Yang H, Qian JM, Li JN |title=[Correlations between gastric Helicobacter pylori infection and colorectal polyps or cancer] |language=Chinese |journal=Zhonghua Nei Ke Za Zhi |volume=58 |issue=2 |pages=139–142 |date=February 2019 |pmid=30704201 |doi=10.3760/cma.j.issn.0578-1426.2019.02.011 |url=}}</ref> Larger polyps can in time become cancerous.<ref name="Zuo"/><ref name="Markowski"/> A modest association of ''H. pylori'' has been made with the development of [[colorectal cancer]]s, but as of 2020 causality had yet to be proved.<ref name="Papastergiou">{{cite journal |vauthors=Papastergiou V, Karatapanis S, Georgopoulos SD |title=Helicobacter pylori and colorectal neoplasia: Is there a causal link? |journal=World J Gastroenterol |volume=22 |issue=2 |pages=649–58 |date=January 2016 |pmid=26811614 |pmc=4716066 |doi=10.3748/wjg.v22.i2.649 |doi-access=free |url=}}</ref><ref name="Zuo">{{cite journal |vauthors=Zuo Y, Jing Z, Bie M, Xu C, Hao X, Wang B |title=Association between Helicobacter pylori infection and the risk of colorectal cancer: A systematic review and meta-analysis |journal=Medicine (Baltimore) |volume=99 |issue=37 |pages=e21832 |date=September 2020 |pmid=32925719 |pmc=7489651 |doi=10.1097/MD.0000000000021832 |url=}}</ref>

=== Signs and symptoms ===
Most people infected with ''H.&nbsp;pylori'' never experience any symptoms or complications, but will have a 10% to 20% risk of developing [[peptic ulcer]]s or a 0.5% to 2% risk of stomach cancer.<ref name="de Brito"/><ref name="Debowski"/> ''H. pylori induced gastritis'' may present as acute gastritis with [[stomach ache]], [[nausea]], and ongoing [[dyspepsia]] (indigestion) that is sometimes accompanied by depression and anxiety.<ref name="de Brito"/><ref name="Cureus">{{cite journal |vauthors=Al Quraan AM, Beriwal N, Sangay P, Namgyal T |title=The Psychotic Impact of Helicobacter pylori Gastritis and Functional Dyspepsia on Depression: A Systematic Review |journal=Cureus |volume=11 |issue=10 |pages=e5956 |date=October 2019 |pmid=31799095 |pmc=6863582 |doi=10.7759/cureus.5956 |doi-access=free |url=}}</ref> Where the gastritis develops into chronic gastritis, or an ulcer, the symptoms are the same and can include [[indigestion]], stomach or abdominal pains, nausea, [[bloating]], [[belching]], feeling hunger in the morning, feeling full too soon, and sometimes [[vomiting]], heartburn, bad breath, and weight loss.<ref name="medlineplus2024">{{cite web |title=Helicobacter Pylori (H. Pylori) Tests: MedlinePlus Medical Test |url=https://medlineplus.gov/lab-tests/helicobacter-pylori-h-pylori-tests/ |website=medlineplus.gov |access-date=16 February 2024 |language=en |archive-date=16 February 2024 |archive-url=https://web.archive.org/web/20240216210728/https://medlineplus.gov/lab-tests/helicobacter-pylori-h-pylori-tests/ |url-status=live }}</ref><ref name="NIDDK">{{cite web |title=Symptoms & Causes of Peptic Ulcers (Stomach or Duodenal Ulcers) - NIDDK |url=https://www.niddk.nih.gov/health-information/digestive-diseases/peptic-ulcers-stomach-ulcers/symptoms-causes |website=National Institute of Diabetes and Digestive and Kidney Diseases |access-date=17 February 2024 |archive-date=17 February 2024 |archive-url=https://web.archive.org/web/20240217131321/https://www.niddk.nih.gov/health-information/digestive-diseases/peptic-ulcers-stomach-ulcers/symptoms-causes |url-status=live }}</ref>

Complications of an ulcer can cause severe signs and symptoms such as black or tarry stool indicative of [[bleeding]] into the stomach or duodenum; blood - either red or coffee-ground colored in vomit; persistent sharp or severe abdominal pain; dizziness, and a fast heartbeat.<ref name="medlineplus2024"/><ref name="NIDDK"/> Bleeding is the most common complication. In cases caused by ''H. pylori'' there was a greater need for [[hemostasis]] often requiring gastric resection.<ref name="Pope">{{cite journal |vauthors=Popa DG, Obleagă CV, Socea B, Serban D, Ciurea ME, Diaconescu M, Vîlcea ID, Meșină C, Mirea C, Florescu DN, Baleanu VD, Comandasu M, Tudosie MS, Tribus LC, Niculescu B |title=Role of Helicobacter pylori in the triggering and evolution of hemorrhagic gastro-duodenal lesions |journal=Exp Ther Med |volume=22 |issue=4 |pages=1147 |date=October 2021 |pmid=34504592 |pmc=8392874 |doi=10.3892/etm.2021.10582 |url=}}</ref> Prolonged bleeding may cause anemia leading to weakness and fatigue. Inflammation of the pyloric antrum, which connects the stomach to the duodenum, is more likely to lead to duodenal ulcers, while inflammation of the [[Body of stomach|corpus]] may lead to a gastric ulcer.

[[Stomach cancer]] can cause nausea, vomiting, diarrhoea, constipation, and unexplained weight loss.<ref>{{cite journal |last1=Al-Azri |first1=Mohammed |last2=Al-Kindi |first2=Jamila |last3=Al-Harthi |first3=Thuraiya |last4=Al-Dahri |first4=Manal |last5=Panchatcharam |first5=Sathiya Murthi |last6=Al-Maniri |first6=Abdullah |date=June 2019 |title=Awareness of Stomach and Colorectal Cancer Risk Factors, Symptoms and Time Taken to Seek Medical Help Among Public Attending Primary Care Setting in Muscat Governorate, Oman |url=http://link.springer.com/10.1007/s13187-017-1266-8 |journal=Journal of Cancer Education |language=en |volume=34 |issue=3 |pages=423–434 |doi=10.1007/s13187-017-1266-8 |pmid=28782080 |s2cid=4017466 |issn=0885-8195 |access-date=20 January 2024 |archive-date=24 February 2024 |archive-url=https://web.archive.org/web/20240224042108/https://link.springer.com/article/10.1007/s13187-017-1266-8 |url-status=live }}</ref> [[Gastric polyp]]s are [[adenoma]]s that are usually asymptomatic and benign, but may be the cause of dyspepsia, heartburn, bleeding from the stomach, and, rarely, gastric outlet obstruction.<ref name="Markowski">{{cite journal | vauthors = Markowski AR, Markowska A, Guzinska-Ustymowicz K | title = Pathophysiological and clinical aspects of gastric hyperplastic polyps | journal = World Journal of Gastroenterology | volume = 22 | issue = 40 | pages = 8883–8891 | date = October 2016 | pmid = 27833379 | pmc = 5083793 | doi = 10.3748/wjg.v22.i40.8883 | doi-access = free }}</ref><ref name="Wu2013">{{cite journal | vauthors = Wu Q, Yang ZP, Xu P, Gao LC, Fan DM | title = Association between Helicobacter pylori infection and the risk of colorectal neoplasia: a systematic review and meta-analysis | journal = Colorectal Disease | volume = 15 | issue = 7 | pages = e352-64 | date = July 2013 | pmid = 23672575 | doi = 10.1111/codi.12284 | s2cid = 5444584 }}</ref> Larger polyps may have [[Malignant transformation|become cancerous]].<ref name="Markowski"/>
[[Colorectal polyp]]s may be the cause of rectal bleeding, anemia, constipation, diarrhea, weight loss, and abdominal pain.<ref name="Soetikno">{{cite journal | vauthors = Soetikno RM, Kaltenbach T, Rouse RV, Park W, Maheshwari A, Sato T, Matsui S, Friedland S | title = Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults | journal = JAMA | volume = 299 | issue = 9 | pages = 1027–35 | date = March 2008 | pmid = 18319413 | doi = 10.1001/jama.299.9.1027 | doi-access = free }}</ref>

==Pathophysiology==
[[Virulence factor]]s help a pathogen to evade the immune response of the host, and to successfully [[colonisation (biology)|colonize]]. The many virulence factors of ''H. pylori'' include its flagella, the production of urease, adhesins, [[serine protease]] [[Peptidase Do|HtrA]] (high temperature requirement A), and the major [[exotoxin]]s [[CagA]] and [[VacA]].<ref name="Baj" /><ref name="Yamaoka2">{{cite book |vauthors=Yamaoka Y, Saruuljavkhlan B, Alfaray RI, Linz B |chapter=Pathogenomics of Helicobacter pylori |title=Helicobacter pylori and Gastric Cancer |series=Current Topics in Microbiology and Immunology |volume=444 |pages=117–155 |date=2023 |pmid=38231217 |doi=10.1007/978-3-031-47331-9_5 |isbn=978-3-031-47330-2 |chapter-url=}}</ref> The presence of VacA and CagA are associated with more [[Pathogenesis|advanced outcomes]].<ref name="Alfarouk">{{cite journal | vauthors = Alfarouk KO, Bashir AH, Aljarbou AN, Ramadan AM, Muddathir AK, AlHoufie ST, Hifny A, Elhassan GO, Ibrahim ME, Alqahtani SS, AlSharari SD, Supuran CT, Rauch C, Cardone RA, Reshkin SJ, Fais S, Harguindey S | title = Helicobacter pylori in Gastric Cancer and Its Management | journal = Frontiers in Oncology | volume = 9 | pages = 75 | date = 22 February 2019 | pmid = 30854333 | pmc = 6395443 | doi = 10.3389/fonc.2019.00075 | doi-access = free }}</ref> CagA is an oncoprotein associated with the development of gastric cancer.<ref name="cancer.gov2023" />
[[File:H pylori virulence factors en.png|thumb|Diagram of ''H. pylori'' and associated [[virulence factor]]s]]
[[File:Ulcer-causing Bacterium (H.Pylori) Crossing Mucus Layer of Stomach.jpg|thumbnail|Diagram showing how ''H.&nbsp;pylori'' reaches the epithelium of the stomach]]
''H.&nbsp;pylori'' infection is associated with [[epigenetically]] reduced efficiency of the [[DNA repair]] machinery, which favors the accumulation of mutations and genomic instability as well as gastric carcinogenesis.<ref name=Santos>{{cite journal | vauthors = Santos JC, Ribeiro ML | title = Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis | journal = World Journal of Gastroenterology | volume = 21 | issue = 30 | pages = 9021–37 | date = August 2015 | pmid = 26290630 | pmc = 4533035 | doi = 10.3748/wjg.v21.i30.9021 | doi-access = free }}</ref> It has been shown that expression of two DNA repair proteins, [[ERCC1]] and [[PMS2]], was severely reduced once ''H.&nbsp;pylori'' infection had progressed to cause [[Indigestion|dyspepsia]].<ref name=Raza2>{{cite journal | vauthors = Raza Y, Ahmed A, Khan A, Chishti AA, Akhter SS, Mubarak M, Bernstein C, Zaitlin B, Kazmi SU | title = Helicobacter pylori severely reduces expression of DNA repair proteins PMS2 and ERCC1 in gastritis and gastric cancer | journal = DNA Repair | volume = 89 | pages = 102836 | date = May 2020 | pmid = 32143126 | doi = 10.1016/j.dnarep.2020.102836 | doi-access = free }}</ref> Dyspepsia occurs in about 20% of infected individuals.<ref name="pmid27239194">{{cite journal | vauthors = Dore MP, Pes GM, Bassotti G, Usai-Satta P | title = Dyspepsia: When and How to Test for Helicobacter pylori Infection | journal = Gastroenterology Research and Practice | volume = 2016 | pages = 8463614 | year = 2016 | pmid = 27239194 | pmc = 4864555 | doi = 10.1155/2016/8463614 | doi-access = free }}</ref> Epigenetically reduced protein expression of DNA repair proteins [[MLH1]], [[O-6-methylguanine-DNA methyltransferase|MGMT]] and [[MRE11A|MRE11]] are also evident. Reduced DNA repair in the presence of increased DNA damage increases carcinogenic mutations and is likely a significant cause of gastric carcinogenesis.<ref name=Raza/><ref name=Muhammad>{{cite journal | vauthors = Muhammad JS, Eladl MA, Khoder G | title = Helicobacter pylori-induced DNA Methylation as an Epigenetic Modulator of Gastric Cancer: Recent Outcomes and Future Direction | journal = Pathogens | volume = 8 | issue = 1 | pages = 23 | date = February 2019 | pmid = 30781778 | pmc = 6471032 | doi = 10.3390/pathogens8010023 | doi-access = free }}</ref><ref name=Noto>{{cite journal | vauthors = Noto JM, Peek RM | title = The role of microRNAs in Helicobacter pylori pathogenesis and gastric carcinogenesis | journal = Frontiers in Cellular and Infection Microbiology | volume = 1 | pages = 21 | date = 2011 | pmid = 22919587 | pmc = 3417373 | doi = 10.3389/fcimb.2011.00021 | doi-access = free }}</ref> These [[Cancer epigenetics|epigenetic alterations]] are due to ''H.&nbsp;pylori''-induced [[CpG site#Promoter CpG hyper/hypo-methylation in cancer|methylation of CpG sites in promoters of genes]]<ref name=Muhammad /> and ''H.&nbsp;pylori''-induced altered expression of multiple [[microRNA]]s.<ref name=Noto/>

Two related mechanisms by which ''H.&nbsp;pylori'' could promote cancer have been proposed. One mechanism involves the enhanced production of [[free radical]]s near ''H.&nbsp;pylori'' and an increased rate of host cell [[mutation]]. The other proposed mechanism has been called a "perigenetic pathway",<ref>{{cite journal | vauthors = Tsuji S, Kawai N, Tsujii M, Kawano S, Hori M | title = Review article: inflammation-related promotion of gastrointestinal carcinogenesis--a perigenetic pathway | journal = Alimentary Pharmacology & Therapeutics | volume = 18 | issue = Suppl 1 | pages = 82–9 | date = July 2003 | pmid = 12925144 | doi = 10.1046/j.1365-2036.18.s1.22.x | s2cid = 22646916 | doi-access = free }}</ref> and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins, such as [[cell adhesion|adhesion]] proteins. ''H.&nbsp;pylori'' has been proposed to induce inflammation and locally high levels of [[tumor necrosis factor]] (TNF), also known as tumor necrosis factor alpha (TNFα)), and/or [[interleukin 6]] (IL-6).<ref>{{cite journal | vauthors = Yu B, de Vos D, Guo X, Peng S, Xie W, Peppelenbosch MP, Fu Y, Fuhler GM | title = IL-6 facilitates cross-talk between epithelial cells and tumor- associated macrophages in Helicobacter pylori-linked gastric carcinogenesis. | journal = Neoplasia | volume = 50 | pages = 100981 | date = April 2024 | pmid = 38422751 | pmc = 10912637 | doi = 10.1016/j.neo.2024.100981 | doi-access = free}}</ref> According to the proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF, can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in [[tumor suppressor gene]]s, such as genes that code for cell adhesion proteins.<ref name="Suganuma">{{cite journal | vauthors = Suganuma M, Yamaguchi K, Ono Y, Matsumoto H, Hayashi T, Ogawa T, Imai K, Kuzuhara T, Nishizono A, Fujiki H | title = TNF-alpha-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells | journal = International Journal of Cancer | volume = 123 | issue = 1 | pages = 117–22 | date = July 2008 | pmid = 18412243 | doi = 10.1002/ijc.23484 | s2cid = 5532769 | doi-access = free }}</ref>

===Flagellum===
The first virulence factor of ''Helicobacter pylori'' that enables colonization is its [[flagellum]].<ref name="Duan">{{cite journal |vauthors=Duan Q, Zhou M, Zhu L, Zhu G |title=Flagella and bacterial pathogenicity |journal=J Basic Microbiol |volume=53 |issue=1 |pages=1–8 |date=January 2013 |pmid=22359233 |doi=10.1002/jobm.201100335 |s2cid=22002199 |url=}}</ref> ''H. pylori'' has from two to seven flagella at [[Lophotrichous|the same polar location]] which gives it a high motility. The flagellar filaments are about 3&nbsp;μm long, and composed of two copolymerized [[flagellin]]s, FlaA and FlaB, coded by the genes ''flaA'', and ''flaB''.<ref name="Kao"/><ref name="Yamaoka2" /> The minor flagellin FlaB is located in the proximal region and the major flagellin FlaA makes up the rest of the flagellum.<ref name="IJMS" /> The flagella are sheathed in a continuation of the bacterial outer membrane which gives protection against the gastric acidity. The sheath is also the location of the origin of the outer membrane vesicles that gives protection to the bacterium from bacteriophages.<ref name="IJMS" />

Flagella motility is provided by the [[proton motive force]] provided by urease-driven hydrolysis allowing [[chemotaxis|chemotactic movements]] towards the less acidic [[pH#pH of various body fluids|pH]] gradient in the mucosa.<ref name="Baj" /> The mucus layer is about 300 [[Micrometre|μm]] thick, and the helical shape of ''H. pylori'' aided by its flagella helps it to burrow through  this layer where it colonises a narrow region of about 25 μm closest to the epithelial cell layer, where the pH is near to neutral. They further colonise the [[gastric pits]] and live in the [[gastric glands]].<ref name="Martínez"/><ref name="IJMS">{{cite journal |vauthors=Nedeljković M, Sastre DE, Sundberg EJ |title=Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure |journal=Int J Mol Sci |volume=22 |issue=14 |date=July 2021 |page=7521 |pmid=34299141 |pmc=8306008 |doi=10.3390/ijms22147521 |doi-access=free |url=}}</ref><ref name="Elbehiry">{{cite journal |vauthors=Elbehiry A, Marzouk E, Aldubaib M, Abalkhail A, Anagreyyah S, Anajirih N, Almuzaini AM, Rawway M, Alfadhel A, Draz A, Abu-Okail A |title=Helicobacter pylori Infection: Current Status and Future Prospects on Diagnostic, Therapeutic and Control Challenges |journal=Antibiotics |volume=12 |issue=2 |date=January 2023 |page=191 |pmid=36830102 |pmc=9952126 |doi=10.3390/antibiotics12020191 |doi-access=free |url=}}</ref> Occasionally the bacteria are found inside the epithelial cells themselves.<ref name="pmid12738380">{{cite journal | vauthors = Petersen AM, Krogfelt KA | title = Helicobacter pylori: an invading microorganism? A review | journal = FEMS Immunology and Medical Microbiology | volume = 36 | issue = 3 | pages = 117–26 | date = May 2003 | pmid = 12738380 | doi = 10.1016/S0928-8244(03)00020-8 | type = Review | doi-access = free }}</ref> The use of [[quorum sensing]] by the bacteria enables the formation of a biofilm which furthers persistent colonisation. In the layers of the biofilm, ''H. pylori'' can escape from the actions of antibiotics, and also be protected from host-immune responses.<ref name=Ali>{{cite journal |vauthors=Ali A, AlHussaini KI |title=Helicobacter pylori: A Contemporary Perspective on Pathogenesis, Diagnosis and Treatment Strategies |journal=Microorganisms |volume=12 |issue=1 |date=January 2024 |page=222 |pmid=38276207 |pmc=10818838 |doi=10.3390/microorganisms12010222 |doi-access=free |url=}}</ref><ref name=Zafer>{{cite journal |vauthors=Zafer MM, Mohamed GA, Ibrahim SR, Ghosh S, Bornman C, Elfaky MA |title=Biofilm-mediated infections by multidrug-resistant microbes: a comprehensive exploration and forward perspectives |journal=Arch Microbiol |volume=206 |issue=3 |pages=101 |date=February 2024 |pmid=38353831 |pmc=10867068 |doi=10.1007/s00203-023-03826-z |bibcode=2024ArMic.206..101Z |url=}}</ref> In the biofilm, ''H. pylori'' can change the flagella to become adhesive structures.<ref name="Sun">{{cite journal |vauthors=Sun Q, Yuan C, Zhou S, Lu J, Zeng M, Cai X, Song H |title=Helicobacter pylori infection: a dynamic process from diagnosis to treatment |journal=Front Cell Infect Microbiol |volume=13 |issue= |pages=1257817 |date=2023 |pmid=37928189 |pmc=10621068 |doi=10.3389/fcimb.2023.1257817 |doi-access=free |url=}}</ref>

===Urease===
[[File:H. pylori urease enzyme diagram.svg|thumb|''H.&nbsp;pylori'' [[urease]] enzyme diagram]]
In addition to using [[chemotaxis]] to avoid areas of high acidity (low pH), ''H.&nbsp;pylori'' also produces large amounts of [[urease]], an [[enzyme]] which breaks down the [[urea]] present in the stomach to produce [[ammonia]] and [[bicarbonate]], which are released into the bacterial cytosol and the surrounding environment, creating a neutral area.<ref name="Lin2">{{cite journal |vauthors=Lin Q, Lin S, Fan Z, Liu J, Ye D, Guo P |title=A Review of the Mechanisms of Bacterial Colonization of the Mammal Gut |journal=Microorganisms |volume=12 |issue=5 |date=May 2024 |page=1026 |pmid=38792855 |pmc=11124445 |doi=10.3390/microorganisms12051026 |doi-access=free |url=}}</ref> The decreased acidity (higher pH) changes the mucus layer from a gel-like state to a more viscous state that makes it easier for the flagella to move the bacteria through the mucosa and attach to the gastric epithelial cells.<ref name="Lin2"/> ''Helicobacter pylori'' is one of the few known types of bacterium that has a [[urea cycle]] which is uniquely configured in the bacterium.<ref name="FEMS">{{cite journal |vauthors=Hernández VM, Arteaga A, Dunn MF |title=Diversity, properties and functions of bacterial arginases |journal=FEMS Microbiol Rev |volume=45 |issue=6 |pages= |date=November 2021 |pmid=34160574 |doi=10.1093/femsre/fuab034 |url=}}</ref> 10% of the cell is of [[nitrogen]], a balance that needs to be maintained. Any excess is stored in urea excreted in the urea cycle.<ref name="FEMS" />

A final stage enzyme in the urea cycle is [[arginase]], an enzyme that is crucial to the pathogenesis of ''H. pylori''. Arginase produces [[ornithine]] and urea, which the enzyme urease breaks down into carbonic acid and ammonia. Urease is the bacterium's most abundant protein, accounting for 10–15% of the bacterium's total protein content. Its expression is not only required for establishing initial colonization in the breakdown of urea to carbonic acid and ammonia, but is also essential for maintaining chronic infection.<ref name="Li">{{cite journal |vauthors=Li S, Zhao W, Xia L, Kong L, Yang L |title=How Long Will It Take to Launch an Effective Helicobacter pylori Vaccine for Humans? |journal=Infect Drug Resist |volume=16 |issue= |pages=3787–3805 |date=2023 |pmid=37342435 |pmc=10278649 |doi=10.2147/IDR.S412361 |doi-access=free |url=}}</ref><ref name="Debowski">{{cite journal | vauthors = Debowski AW, Walton SM, Chua EG, Tay AC, Liao T, Lamichhane B, Himbeck R, Stubbs KA, Marshall BJ, Fulurija A, Benghezal M | title = Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection | journal = PLOS Pathogens | volume = 13 | issue = 6 | pages = e1006464 | date = June 2017 | pmid = 28644872 | pmc = 5500380 | doi = 10.1371/journal.ppat.1006464 | doi-access = free }}</ref> Ammonia reduces stomach acidity, allowing the bacteria to become locally established. Arginase promotes the persistence of infection by consuming arginine; arginine is used by macrophages to produce nitric oxide, which has a strong antimicrobial effect.<ref name="FEMS" /><ref name="George">{{cite journal | vauthors = George G, Kombrabail M, Raninga N, Sau AK | title = Arginase of Helicobacter Gastric Pathogens Uses a Unique Set of Non-catalytic Residues for Catalysis | journal = Biophysical Journal | volume = 112 | issue = 6 | pages = 1120–1134 | date = March 2017 | pmid = 28355540 | pmc = 5376119 | doi = 10.1016/j.bpj.2017.02.009 | bibcode = 2017BpJ...112.1120G }}</ref> The ammonia produced to regulate [[pH]] is toxic to epithelial cells.<ref>{{cite journal | vauthors = Smoot DT | title = How does Helicobacter pylori cause mucosal damage? Direct mechanisms | journal = Gastroenterology | volume = 113 | issue = 6 Suppl | pages = S31-4; discussion S50 | date = December 1997 | pmid = 9394757 | doi = 10.1016/S0016-5085(97)80008-X | doi-access = free }}</ref>

===Adhesins===
''H. pylori'' must make attachment with the epithelial cells to prevent its being swept away with the constant movement and renewal of the mucus. To give them this adhesion, [[Bacterial outer membrane#Outer membrane proteins|bacterial outer membrane proteins]] as virulence factors called [[bacterial adhesin|adhesins]] are produced.<ref name="Doohan">{{cite journal |vauthors=Doohan D, Rezkitha YA, Waskito LA, Yamaoka Y, Miftahussurur M |title=Helicobacter pylori BabA-SabA Key Roles in the Adherence Phase: The Synergic Mechanism for Successful Colonization and Disease Development |journal=Toxins |volume=13 |issue=7 |date=July 2021 |page=485 |pmid=34357957 |pmc=8310295 |doi=10.3390/toxins13070485 |doi-access=free |url=}}</ref> BabA (blood group antigen binding adhesin) is most important during initial colonization, and SabA (sialic acid binding adhesin) is important in persistence. BabA attaches to glycans and mucins in the epithelium.<ref name="Doohan"/> BabA (coded for by the ''babA2'' gene) also binds to the [[Lewis antigen system|Lewis b antigen]] displayed on the surface of the epithelial cells.<ref name="Rad">{{cite journal |last1=Rad |first1=Roland |last2=Gerhard |first2=Markus |last3=Lang |first3=Roland |last4=Schöniger |first4=Martin |last5=Rösch |first5=Thomas |last6=Schepp |first6=Wolfgang |last7=Becker |first7=Ingrid |last8=Wagner |first8=Hermann |last9=Prinz |first9=Christian |title=The Helicobacter pylori Blood Group Antigen-Binding Adhesin Facilitates Bacterial Colonization and Augments a Nonspecific Immune Response |journal=The Journal of Immunology |date=15 March 2002 |volume=168 |issue=6 |pages=3033–3041 |doi=10.4049/jimmunol.168.6.3033|pmid=11884476 |doi-access=free }}</ref> Adherence via BabA is acid sensitive and can be fully reversed by a decreased pH. It has been proposed that BabA's acid responsiveness enables adherence while also allowing an effective escape from an unfavorable environment such as a low pH that is harmful to the organism.<ref>{{cite journal | vauthors = Bugaytsova JA, Björnham O, Chernov YA, Gideonsson P, Henriksson S, Mendez M, Sjöström R, Mahdavi J, Shevtsova A, Ilver D, Moonens K, Quintana-Hayashi MP, Moskalenko R, Aisenbrey C, Bylund G, Schmidt A, Åberg A, Brännström K, Königer V, Vikström S, Rakhimova L, Hofer A, Ögren J, Liu H, Goldman MD, Whitmire JM, Ådén J, Younson J, Kelly CG, Gilman RH, Chowdhury A, Mukhopadhyay AK, Nair GB, Papadakos KS, Martinez-Gonzalez B, Sgouras DN, Engstrand L, Unemo M, Danielsson D, Suerbaum S, Oscarson S, Morozova-Roche LA, Olofsson A, Gröbner G, Holgersson J, Esberg A, Strömberg N, Landström M, Eldridge AM, Chromy BA, Hansen LM, Solnick JV, Lindén SK, Haas R, Dubois A, Merrell DS, Schedin S, Remaut H, Arnqvist A, Berg DE, Borén T | title = Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence | journal = Cell Host & Microbe | volume = 21 | issue = 3 | pages = 376–389 | date = March 2017 | pmid = 28279347 | pmc = 5392239 | doi = 10.1016/j.chom.2017.02.013 }}</ref> SabA (coded for by the ''sabA'' gene) binds to increased levels of [[sialyl-Lewis x|sialyl-Lewis <sup>X</sup>]] antigen expressed on gastric mucosa.<ref name="pmid12142529">{{cite journal | vauthors = Mahdavi J, Sondén B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadström T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarström L, Borén T | title = Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation | journal = Science | volume = 297 | issue = 5581 | pages = 573–8 | date = July 2002 | pmid = 12142529 | pmc = 2570540 | doi = 10.1126/science.1069076 | bibcode = 2002Sci...297..573M }}</ref>

===Cholesterol glucoside===
The outer membrane contains ''cholesterol glucoside'', a sterol glucoside that ''H. pylori'' [[Glycosylation|glycosylates]] from the [[cholesterol]] in the gastric gland cells, and inserts it into its outer membrane.<ref name="Testerman">{{cite journal | vauthors = Testerman TL, Morris J | title = Beyond the stomach: an updated view of Helicobacter pylori pathogenesis, diagnosis, and treatment | journal = World Journal of Gastroenterology | volume = 20 | issue = 36 | pages = 12781–808 | date = September 2014 | pmid = 25278678 | pmc = 4177463 | doi = 10.3748/wjg.v20.i36.12781 | type = Review | doi-access = free }}</ref> This cholesterol glucoside is important for membrane stability, morphology and immune evasion, and is rarely found in other bacteria.<ref name="Zhang">{{cite journal |vauthors=Zhang L, Xie J |title=Biosynthesis, structure and biological function of cholesterol glucoside in Helicobacter pylori: A review |journal=Medicine (Baltimore) |volume=102 |issue=36 |pages=e34911 |date=September 2023 |pmid=37682174 |pmc=10489377 |doi=10.1097/MD.0000000000034911 |url=}}</ref><ref name="Ridyard">{{cite journal |vauthors=Ridyard KE, Overhage J |title=The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent |journal=Antibiotics |volume=10 |issue=6 |date=May 2021 |page=650 |pmid=34072318 |pmc=8227053 |doi=10.3390/antibiotics10060650 |doi-access=free |url=}}</ref>

The enzyme responsible for this is ''cholesteryl α-glucosyltransferase'' (αCgT or Cgt), encoded by the ''HP0421'' gene.<ref name="Hsu">{{cite journal |vauthors=Hsu CY, Yeh JY, Chen CY, Wu HY, Chiang MH, Wu CL, Lin HJ, Chiu CH, Lai CH |title=Helicobacter pylori cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells |journal=Virulence |volume=12 |issue=1 |pages=2341–2351 |date=December 2021 |pmid=34506250 |pmc=8437457 |doi=10.1080/21505594.2021.1969171 |url=}}</ref> A major effect of the depletion of host cholesterol by Cgt is to disrupt cholesterol-rich [[lipid raft]]s in the epithelial cells. Lipid rafts are involved in cell signalling and their disruption causes a reduction in the immune inflammatory response, particularly by reducing [[interferon gamma]].<ref name="Morey">{{cite journal |vauthors=Morey P, Pfannkuch L, Pang E, Boccellato F, Sigal M, Imai-Matsushima A, Dyer V, Koch M, Mollenkopf HJ, Schlaermann P, Meyer TF |title=Helicobacter pylori Depletes Cholesterol in Gastric Glands to Prevent Interferon Gamma Signaling and Escape the Inflammatory Response |journal=Gastroenterology |volume=154 |issue=5 |pages=1391–1404.e9 |date=April 2018 |pmid=29273450 |doi=10.1053/j.gastro.2017.12.008 |url=|hdl=21.11116/0000-0001-3B12-9 |hdl-access=free }}</ref> Cgt is also secreted by the type IV secretion system, and is secreted in a selective way so that gastric niches where the pathogen can thrive are created.<ref name="Hsu" /> Its lack has been shown to give vulnerability from environmental stress to bacteria, and also to disrupt CagA-mediated interactions.<ref name="Testerman" />

===Catalase===
Colonization induces an intense anti-inflammatory response as a first-line immune system defence. Phagocytic leukocytes and monocytes infiltrate the site of infection, and antibodies are produced.<ref name="Ramarao">{{cite journal |vauthors=Ramarao N, Gray-Owen SD, Meyer TF |title=Helicobacter pylori induces but survives the extracellular release of oxygen radicals from professional phagocytes using its catalase activity |journal=Mol Microbiol |volume=38 |issue=1 |pages=103–13 |date=October 2000 |pmid=11029693 |doi=10.1046/j.1365-2958.2000.02114.x |url=|hdl=11858/00-001M-0000-000E-C7AD-8 |hdl-access=free }}</ref> ''H. pylori'' is able to adhere to the surface of the phagocytes and impede their action. This is responded to by the phagocyte in the generation and release of oxygen metabolites into the surrounding space. ''H. pylori'' can survive this response by the activity of [[catalase]] at its attachment to the phagocytic cell surface. Catalase decomposes hydrogen peroxide into water and oxygen, protecting the bacteria from toxicity. Catalase has been shown to almost completely inhibit the phagocytic oxidative response.<ref name="Ramarao" /> It is coded for by the gene ''katA''.<ref name="UniProt1">{{cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/P77872/entry |website=www.uniprot.org |access-date=20 March 2024}}</ref>

===Tipα===
TNF-inducing protein alpha (Tipα) is a carcinogenic protein encoded by ''HP0596'' unique to ''H. pylori'' that induces the expression of [[tumor necrosis factor]].<ref name="Suganuma"/><ref name="UniProt">{{cite web |title=TNF-alpha inducing protein |url=https://www.uniprot.org/uniprotkb/O25318/entry |website=www.uniprot.org |access-date=8 April 2024}}</ref> Tipα enters gastric cancer cells where it binds to cell surface [[nucleolin]], and induces the expression of [[vimentin]]. Vimentin is important in the [[epithelial–mesenchymal transition]] associated with the progression of tumors.<ref name="IJoC">{{cite journal |last1=Watanabe |first1=Tatsuro |last2=Takahashi |first2=Atsushi |last3=Suzuki |first3=Kaori |last4=Kurusu-Kanno |first4=Miki |last5=Yamaguchi |first5=Kensei |last6=Fujiki |first6=Hirota |last7=Suganuma |first7=Masami |title=Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori: Cell migration induced by Tipα of H. pylori |journal=International Journal of Cancer |date=15 May 2014 |volume=134 |issue=10 |pages=2373–2382 |doi=10.1002/ijc.28582|pmid=24249671 }}</ref>

===CagA===
'''CagA''' (cytotoxin-associated antigen A) is a major [[virulence factor]] for ''H.&nbsp;pylori'', an [[oncoprotein]] that is encoded by the ''cagA'' gene. Bacterial strains with the ''cagA'' gene are associated with the ability to cause ulcers, MALT lymphomas, and gastric cancer.<ref name="Wallden">{{cite journal |vauthors=Wallden K, Rivera-Calzada A, Waksman G |title=Type IV secretion systems: versatility and diversity in function |journal=Cell Microbiol |volume=12 |issue=9 |pages=1203–12 |date=September 2010 |pmid=20642798 |pmc=3070162 |doi=10.1111/j.1462-5822.2010.01499.x |url=}}</ref><ref name="pmid11283049">{{cite journal | vauthors = Broutet N, Marais A, Lamouliatte H, de Mascarel A, Samoyeau R, Salamon R, Mégraud F | title = cagA Status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia | journal = Journal of Clinical Microbiology | volume = 39 | issue = 4 | pages = 1319–22 | date = April 2001 | pmid = 11283049 | pmc = 87932 | doi = 10.1128/JCM.39.4.1319-1322.2001 }}</ref> The ''cagA'' gene codes for a relatively long (1186-[[amino acid]]) protein. The ''cag'' [[pathogenicity island]] (PAI) has about 30 genes, part of which code for a complex [[type IV secretion system]] (T4SS or TFSS). The low [[GC-content]] of the ''cag'' PAI relative to the rest of the ''Helicobacter'' genome suggests the island was acquired by [[horizontal gene transfer|horizontal transfer]] from another bacterial species.<ref name="Tomb 1997"/> The [[serine protease]] [[Peptidase Do|HtrA]] also plays a major role in the pathogenesis of ''H.&nbsp;pylori''. The HtrA protein enables the bacterium to transmigrate across the host cells' epithelium, and is also needed for the translocation of CagA.<ref name="Zawilak-Pawlik2019">{{cite journal | vauthors = Zawilak-Pawlik A, Zarzecka U, Żyła-Uklejewicz D, Lach J, Strapagiel D, Tegtmeyer N, Böhm M, Backert S, Skorko-Glonek J | title = Establishment of serine protease htrA mutants in Helicobacter pylori is associated with secA mutations | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 11794 | date = August 2019 | pmid = 31409845 | pmc = 6692382 | doi = 10.1038/s41598-019-48030-6 | bibcode = 2019NatSR...911794Z }}</ref>

The virulence of ''H.&nbsp;pylori'' may be increased by genes of the ''cag'' pathogenicity island; about 50–70% of ''H.&nbsp;pylori'' strains in Western countries carry it.<ref name="Peek 2006">{{cite journal | vauthors = Peek RM, Crabtree JE | title = Helicobacter infection and gastric neoplasia | journal = The Journal of Pathology | volume = 208 | issue = 2 | pages = 233–48 | date = January 2006 | pmid = 16362989 | doi = 10.1002/path.1868 | s2cid = 31718278 | doi-access = free }}</ref> Western people infected with strains carrying the ''cag'' PAI have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island.<ref name="Kusters2006"/> Following attachment of ''H.&nbsp;pylori'' to stomach epithelial cells, the type IV secretion system expressed by the ''cag'' PAI "injects" the [[inflammation]]-inducing agent, peptidoglycan, from their own [[cell wall]]s into the epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic [[pattern recognition receptor]] (immune sensor) Nod1, which then stimulates expression of [[cytokines]] that promote inflammation.<ref>{{cite journal | vauthors = Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL | title = Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island | journal = Nature Immunology | volume = 5 | issue = 11 | pages = 1166–74 | date = November 2004 | pmid = 15489856 | doi = 10.1038/ni1131 | s2cid = 2898805 }}</ref>

The type-IV [[secretion]] apparatus also injects the ''cag'' PAI-encoded protein CagA into the stomach's epithelial cells, where it disrupts the [[cytoskeleton]], adherence to adjacent cells, intracellular signaling, [[Epithelial polarity|cell polarity]], and other cellular activities.<ref name="Backert 2008">{{cite journal | vauthors = Backert S, Selbach M | title = Role of type IV secretion in Helicobacter pylori pathogenesis | journal = Cellular Microbiology | volume = 10 | issue = 8 | pages = 1573–81 | date = August 2008 | pmid = 18410539 | doi = 10.1111/j.1462-5822.2008.01156.x | s2cid = 37626 | doi-access = free }}</ref> Once inside the cell, the CagA protein is [[Phosphorylation|phosphorylated]] on [[Protein kinase#Tyrosine-specific protein kinases|tyrosine residues]] by a host cell membrane-associated [[tyrosine kinase]] (TK). CagA then allosterically activates [[protein tyrosine phosphatase]]/[[protooncogene]] [[Shp2]].<ref name="Hatakeyama">{{cite journal | vauthors = Hatakeyama M | title = Oncogenic mechanisms of the Helicobacter pylori CagA protein | journal = Nature Reviews. Cancer | volume = 4 | issue = 9 | pages = 688–94 | date = September 2004 | pmid = 15343275 | doi = 10.1038/nrc1433 | s2cid = 1218835 }}</ref>
These proteins are directly toxic to cells lining the stomach and signal strongly to the immune system that an invasion is under way. As a result of the bacterial presence, neutrophils and macrophages set up residence in the tissue to fight the bacteria assault.<ref>{{cite journal | doi=10.1007/s12156-008-0068-y | title=The role of Helicobacter pylori in the pathogenesis of gastric malignancies | date=2008 | journal=Oncology Reviews | volume=2 | issue=3 | pages=131–140 | vauthors = Kim W, Moss SF }}</ref> Pathogenic strains of ''H.&nbsp;pylori'' have been shown to activate the [[epidermal growth factor receptor]] (EGFR), a [[membrane protein]] with a TK [[protein domain|domain]]. Activation of the EGFR by ''H.&nbsp;pylori'' is associated with altered [[signal transduction]] and [[gene expression]] in host epithelial cells that may contribute to pathogenesis. A [[C-terminus|C-terminal]] region of the CagA protein (amino acids 873–1002) has also been suggested to be able to regulate host cell [[Transcription (genetics)|gene transcription]], independent of protein tyrosine phosphorylation.<ref name="pmid11283049"/> A great deal of diversity exists between strains of ''H.&nbsp;pylori'', and the strain that infects a person can predict the outcome.

===VacA===
'''VacA''' (vacuolating cytotoxin autotransporter) is another major virulence factor encoded by the ''vacA'' gene.<ref name="UniProt2">{{cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/Q48245/entry |website=www.uniprot.org |access-date=21 March 2024}}</ref> All strains of ''H. pylori'' carry this gene but there is much diversity, and only 50% produce the encoded cytotoxin.<ref name="Li"/><ref name="Alzahrani"/> The four main subtypes of ''vacA'' are ''s1/m1, s1/m2, s2/m1,'' and ''s2/m2''. ''s1/m1'' and ''s1/m2'' are known to cause an increased risk of gastric cancer.<ref>{{cite journal | vauthors = Miehlke S, Yu J, Schuppler M, Frings C, Kirsch C, Negraszus N, Morgner A, Stolte M, Ehninger G, Bayerdörffer E | title = Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease | journal = The American Journal of Gastroenterology | volume = 96 | issue = 4 | pages = 1008–13 | date = April 2001 | doi = 10.1111/j.1572-0241.2001.03685.x | pmid = 11316139 | s2cid = 24024542 | url = http://journals.lww.com/10.1111/j.1572-0241.2001.03685.x | access-date = 24 June 2020 | archive-date = 23 February 2022 | archive-url = https://web.archive.org/web/20220223203948/https://journals.lww.com/ajg/Abstract/2001/04000/Helicobacter_Pylori_Vaca,_Icea,andCagaStatus_and.17.aspx | url-status = live }}</ref> VacA is an oligomeric protein complex that causes a progressive vacuolation in the epithelial cells leading to their death.<ref name="Hisatsune"/> The vacuolation has also been associated with promoting intracellular reservoirs of ''H. pylori'' by disrupting the calcium channel cell membrane [[MCOLN1|TRPML1]].<ref>{{cite journal | vauthors = Capurro MI, Greenfield LK, Prashar A, Xia S, Abdullah M, Wong H, Zhong XZ, Bertaux-Skeirik N, Chakrabarti J, Siddiqui I, O'Brien C, Dong X, Robinson L, Peek RM, Philpott DJ, Zavros Y, Helmrath M, Jones NL | title = VacA generates a protective intracellular reservoir for Helicobacter pylori that is eliminated by activation of the lysosomal calcium channel TRPML1 | journal = Nature Microbiology | volume = 4 | issue = 8 | pages = 1411–1423 | date = August 2019 | pmid = 31110360 | pmc = 6938649 | doi = 10.1038/s41564-019-0441-6 }}</ref> VacA has been shown to increase the levels of [[Cyclooxygenase-2|COX2]], an up-regulation that increases the production of a [[prostaglandin]] indicating a strong host cell inflammatory response.<ref name="Hisatsune">{{cite journal |vauthors=Hisatsune J, Yamasaki E, Nakayama M, Shirasaka D, Kurazono H, Katagata Y, Inoue H, Han J, Sap J, Yahiro K, Moss J, Hirayama T |title=Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells |journal=Infect Immun |volume=75 |issue=9 |pages=4472–81 |date=September 2007 |pmid=17591797 |pmc=1951161 |doi=10.1128/IAI.00500-07 |url=}}</ref><ref>{{cite journal | vauthors = Sajib S, Zahra FT, Lionakis MS, German NA, Mikelis CM | title = Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions | journal = Angiogenesis | volume = 21 | issue = 1 | pages = 1–14 | date = February 2018 | pmid = 29110215 | doi = 10.1007/s10456-017-9583-4 | s2cid = 3346742 }}</ref>

===Outer membrane proteins and vesicles===
About 4% of the genome encodes for [[outer membrane proteins]] that can be grouped into five families.<ref name="da Costa">{{cite journal |vauthors=da Costa DM, Pereira Edos S, Rabenhorst SH |title=What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases |journal=World J Gastroenterol |volume=21 |issue=37 |pages=10563–72 |date=October 2015 |pmid=26457016 |pmc=4588078 |doi=10.3748/wjg.v21.i37.10563 |doi-access=free |url=}}</ref> The largest family includes [[bacterial adhesin]]s. The other four families are [[Porin (protein)|porin]]s, iron transporters, [[flagella|flagellum]]-associated proteins, and proteins of unknown function. Like other typical gram-negative bacteria, the outer membrane of ''H.&nbsp;pylori'' consists of [[phospholipids]] and [[lipopolysaccharide]] (LPS). The [[Lipopolysaccharide#O-antigen|O-antigen]] of LPS may be [[fucose|fucosylated]] and mimic [[Lewis antigen system|Lewis blood group antigens]] found on the gastric epithelium.<ref name="Kusters2006"/>

''H. pylori'' forms blebs from the outer membrane that pinch off as [[outer membrane vesicle]]s to provide an alternative delivery system for virulence factors including CagA.<ref name="Testerman"/>

A ''Helicobacter'' [[cysteine-rich protein]] HcpA is known to trigger an immune response, causing inflammation.<ref name="pmid19393649">{{cite journal | vauthors = Dumrese C, Slomianka L, Ziegler U, Choi SS, Kalia A, Fulurija A, Lu W, Berg DE, Benghezal M, Marshall B, Mittl PR | title = The secreted Helicobacter cysteine-rich protein A causes adherence of human monocytes and differentiation into a macrophage-like phenotype | journal = FEBS Letters | volume = 583 | issue = 10 | pages = 1637–43 | date = May 2009 | pmid = 19393649 | pmc = 2764743 | doi = 10.1016/j.febslet.2009.04.027 | bibcode = 2009FEBSL.583.1637D }}</ref> 
A ''Helicobacter pylori'' virulence factor ''DupA'' is associated with the development of duodenal ulcers.<ref name="Alam">{{cite journal |vauthors=Alam J, Sarkar A, Karmakar BC, Ganguly M, Paul S, Mukhopadhyay AK |title=Novel virulence factor dupA of Helicobacter pylori as an important risk determinant for disease manifestation: An overview |journal=World J Gastroenterol |volume=26 |issue=32 |pages=4739–4752 |date=August 2020 |pmid=32921954 |pmc=7459207 |doi=10.3748/wjg.v26.i32.4739 |doi-access=free |url=}}</ref>

===Mechanisms of tolerance===
The need for survival has led to the development of different mechanisms of tolerance that enable the persistence of ''H. pylori''.<ref name="Trastoy">{{cite journal |vauthors=Trastoy R, Manso T, Fernández-García L, Blasco L, Ambroa A, Pérez Del Molino ML, Bou G, García-Contreras R, Wood TK, Tomás M |title=Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments |journal=Clin Microbiol Rev |volume=31 |issue=4 |pages= |date=October 2018 |pmid=30068737 |pmc=6148185 |doi=10.1128/CMR.00023-18 |url=}}</ref> These mechanisms can also help to overcome the effects of antibiotics.<ref name="Trastoy" /> ''H. pylori'' has to not only survive the harsh gastric acidity but also the sweeping of mucus by continuous [[peristalsis]], and [[phagocytic]] attack accompanied by the release of [[reactive oxygen species]].<ref>{{cite journal | vauthors = Olczak AA, Olson JW, Maier RJ | title = Oxidative-stress resistance mutants of Helicobacter pylori | journal = Journal of Bacteriology | volume = 184 | issue = 12 | pages = 3186–93 | date = June 2002 | pmid = 12029034 | pmc = 135082 | doi = 10.1128/JB.184.12.3186-3193.2002 }}</ref>  All organisms encode genetic programs for response to stressful conditions including those that cause DNA damage.<ref name=Dorer /> Stress conditions activate bacterial response mechanisms that are regulated by proteins expressed by [[regulator gene]]s.<ref name="Trastoy" /> The [[oxidative stress]] can induce potentially lethal mutagenic [[DNA adduct]]s in its genome. Surviving this [[DNA damage]] is supported by [[Genetic transformation|transformation]]-mediated [[homologous recombination|recombinational repair]], that contributes to successful colonization.<ref>{{cite journal | vauthors = O'Rourke EJ, Chevalier C, Pinto AV, Thiberge JM, Ielpi L, Labigne A, Radicella JP | title = Pathogen DNA as target for host-generated oxidative stress: role for repair of bacterial DNA damage in Helicobacter pylori colonization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 5 | pages = 2789–94 | date = March 2003 | pmid = 12601164 | pmc = 151419 | doi = 10.1073/pnas.0337641100 | bibcode = 2003PNAS..100.2789O | doi-access = free }}</ref><ref>{{cite journal | vauthors = Michod RE, Bernstein H, Nedelcu AM | title = Adaptive value of sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 8 | issue = 3 | pages = 267–85 | date = May 2008 | pmid = 18295550 | doi = 10.1016/j.meegid.2008.01.002 | bibcode = 2008InfGE...8..267M }}</ref> ''H.&nbsp;pylori'' is naturally competent for transformation. While many organisms are competent only under certain environmental conditions, such as starvation, ''H.&nbsp;pylori'' is competent throughout logarithmic growth.<ref name=Dorer>{{cite journal | vauthors = Dorer MS, Fero J, Salama NR | title = DNA damage triggers genetic exchange in Helicobacter pylori | journal = PLOS Pathogens | volume = 6 | issue = 7 | pages = e1001026 | date = July 2010 | pmid = 20686662 | pmc = 2912397 | doi = 10.1371/journal.ppat.1001026 | editor1-last = Blanke | editor1-first = Steven R. | doi-access = free }}</ref>

[[Transformation (genetics)|Transformation]] (the transfer of DNA from one bacterial cell to another through the intervening medium) appears to be part of an adaptation for [[DNA repair]].<ref name=Dorer/> [[Homologous recombination]] is required for repairing [[double-strand break]]s (DSBs). The AddAB helicase-nuclease complex resects DSBs and loads [[RecA]] onto single-strand DNA (ssDNA), which then mediates strand exchange, leading to homologous recombination and repair. The requirement of RecA plus AddAB for efficient gastric colonization suggests that ''H.&nbsp;pylori'' is either exposed to double-strand DNA damage that must be repaired or requires some other recombination-mediated event. In particular, natural transformation is increased by DNA damage in ''H.&nbsp;pylori'', and a connection exists between the DNA damage response and DNA uptake in ''H.&nbsp;pylori''.<ref name=Dorer />  This natural competence contributes to the persistence of ''H.&nbsp;pylori''. ''H. pylori'' has much greater rates of recombination and mutation than other bacteria.<ref name="Yamaoka"/>  Genetically different strains can be found in the same host, and also in different regions of the stomach.<ref name="Ailloud">{{cite journal |vauthors=Ailloud F, Didelot X, Woltemate S, Pfaffinger G, Overmann J, Bader RC, Schulz C, Malfertheiner P, Suerbaum S |title=Within-host evolution of Helicobacter pylori shaped by niche-specific adaptation, intragastric migrations and selective sweeps |journal=Nat Commun |volume=10 |issue=1 |pages=2273 |date=May 2019 |pmid=31118420 |pmc=6531487 |doi=10.1038/s41467-019-10050-1 |bibcode=2019NatCo..10.2273A |url=}}</ref> An overall response to multiple stressors can result from an interaction of the mechanisms.<ref name="Trastoy" />

[[RuvABC]] proteins are essential to the process of recombinational repair, since they resolve intermediates in this process termed [[Holliday junction]]s. ''H.&nbsp;pylori'' mutants that are defective in RuvC have increased sensitivity to DNA-damaging agents and to oxidative stress, exhibit reduced survival within macrophages, and are unable to establish successful infection in a mouse model.<ref>{{cite journal | vauthors = Loughlin MF, Barnard FM, Jenkins D, Sharples GJ, Jenks PJ | title = Helicobacter pylori mutants defective in RuvC Holliday junction resolvase display reduced macrophage survival and spontaneous clearance from the murine gastric mucosa | journal = Infection and Immunity | volume = 71 | issue = 4 | pages = 2022–31 | date = April 2003 | pmid = 12654822 | pmc = 152077 | doi = 10.1128/IAI.71.4.2022-2031.2003 }}</ref> Similarly, RecN protein plays an important role in DSB repair.<ref name=Wang>{{cite journal | vauthors = Wang G, Maier RJ | title = Critical role of RecN in recombinational DNA repair and survival of Helicobacter pylori | journal = Infection and Immunity | volume = 76 | issue = 1 | pages = 153–60 | date = January 2008 | pmid = 17954726 | pmc = 2223656 | doi = 10.1128/IAI.00791-07 }}</ref> An ''H.&nbsp;pylori'' recN mutant displays an attenuated ability to colonize mouse stomachs, highlighting the importance of recombinational DNA repair in survival of ''H.&nbsp;pylori'' within its host.<ref name=Wang/>

====Biofilm====
An effective sustained colonization response is the formation of a [[biofilm]].
Having first adhered to cellular surfaces, the bacteria produce and secrete [[extracellular polymeric substance]] (EPS). EPS consists largely of [[biopolymer]]s and provides the framework for the biofilm structure.<ref name="Lin2"/> ''H. pylori'' helps the biofilm formation by altering its flagella into adhesive structures that provide adhesion between the cells.<ref name="Sun"/> Layers of aggregated bacteria as microcolonies accumulate to thicken the biofilm.

The matrix of EPS prevents the entry of antibiotics and immune cells, and provides protection from heat and competition from other microorganisms.<ref name="Lin2"/> Channels form between the cells in the biofilm matrix allowing the transport of nutrients, enzymes, metabolites, and waste.<ref name="Lin2"/> Cells in the deep layers may be nutritionally deprived and enter into the coccoid dormant-like state.<ref name="Bahmaninejad">{{cite journal |vauthors=Bahmaninejad P, Ghafourian S, Mahmoudi M, Maleki A, Sadeghifard N, Badakhsh B |title=Persister cells as a possible cause of antibiotic therapy failure in Helicobacter pylori |journal=JGH Open |volume=5 |issue=4 |pages=493–497 |date=April 2021 |pmid=33860100 |pmc=8035453 |doi=10.1002/jgh3.12527 |url=}}</ref><ref name="Cammarota">{{cite journal |last1=Cammarota |first1=G. |last2=Sanguinetti |first2=M. |last3=Gallo |first3=A. |last4=Posteraro |first4=B. |title=Review article: biofilm formation by H elicobacter pylori as a target for eradication of resistant infection |url=https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2012.05165.x |journal=Alimentary Pharmacology & Therapeutics |access-date=3 March 2024 |pages=222–230 |language=en |doi=10.1111/j.1365-2036.2012.05165.x |date=August 2012|volume=36 |issue=3 |pmid=22650647 |s2cid=24026187 }}</ref> By changing the shape of the bacterium to a coccoid form, the exposure of [[Lipopolysaccharide|LPS]] (targeted by antibiotics) becomes limited, and so evades detection by the immune system.<ref name="Shadvar"/> It has also been shown that the ''cag'' pathogenicity island remains intact in the coccoid form.<ref name="Shadvar"/> Some of these antibiotic resistant cells may remain in the host as [[persister cell]]s. Following eradication, the persister cells can cause a recurrence of the infection.<ref name="Bahmaninejad"/><ref name="Cammarota"/> Bacteria can detach from the biofilm to relocate and colonize elsewhere in the stomach to form other biofilms.<ref name="Lin2"/>

==Diagnosis==
[[Image:pylorigastritis.jpg|thumb|right|''H.&nbsp;pylori'' colonized on the surface of regenerative epithelium ([[Warthin–Starry stain|Warthin-Starry silver stain]])]]
Colonization with ''H.&nbsp;pylori'' does not always lead to disease, but is associated with a number of [[stomach disease]]s.<ref name="Kusters2006"/> Testing is recommended in cases of [[peptic ulcer disease]] or low-grade gastric [[MALT lymphoma]]; after [[endoscopy|endoscopic]] resection of early [[gastric cancer]]; for first-degree relatives with gastric cancer, and in certain cases of indigestion. Other indications that prompt testing for ''H. pylori'' include long term [[aspirin]] or other [[non-steroidal anti-inflammatory]] use, unexplained [[iron deficiency anemia]], or in cases of [[immune thrombocytopenic purpura]].<ref name="Crowe 2019">{{cite journal |last1=Crowe |first1=Sheila E. |title=Helicobacter pylori Infection |journal=New England Journal of Medicine |date=21 March 2019 |volume=380 |issue=12 |pages=1158–1165 |doi=10.1056/NEJMcp1710945|pmid=30893536 |s2cid=84843669 }}</ref> Several methods of testing exist, both invasive and non-invasive.

Non-invasive tests for ''H.&nbsp;pylori'' infection include [[serological test]]s for [[antibodies]], [[stool test]]s, and [[urea breath test]]s. Carbon urea breath tests include the use of [[carbon-13]], or a radioactive [[carbon-14]] producing a labelled carbon dioxide that can be detected in the breath.<ref name="Jambi">{{cite journal |last1=Jambi |first1=LK |title=Systematic Review and Meta-Analysis on the Sensitivity and Specificity of (13)C/(14)C-Urea Breath Tests in the Diagnosis of Helicobacter pylori Infection. |journal=Diagnostics |date=7 October 2022 |volume=12 |issue=10 |page=2428 |doi=10.3390/diagnostics12102428 |doi-access=free |pmid=36292117|pmc=9600925 }}</ref> Carbon urea breath tests have a high [[sensitivity and specificity]] for the diagnosis of ''H. pylori''.<ref name="Jambi"/>

Proton-pump inhibitors and antibiotics should be discontinued for at least 30 days prior to testing for ''H. pylori'' infection or eradication, as both agents inhibit ''H. pylori'' growth and may lead to false negative results.<ref name="Crowe 2019" /> Testing to confirm eradication is recommended 30 days or more after completion of treatment for ''H. pylori'' infection. ''H. pylori'' breath testing or stool antigen testing are both reasonable tests to confirm eradication.<ref name="Crowe 2019" /> ''H. pylori'' serologic testing, including [[Immunoglobulin G|IgG antibodies]], are not recommended as a test of eradication as they may remain elevated for years after successful treatment of infection.<ref name="Crowe 2019" />

An endoscopic biopsy is an invasive means to test for ''H.&nbsp;pylori'' infection. Low-level infections can be missed by biopsy, so multiple samples are recommended. The most accurate method for detecting ''H.&nbsp;pylori'' infection is with a [[histological]] examination from two sites after endoscopic [[biopsy]], combined with either a [[rapid urease test]] or microbial culture.<ref name="Logan">{{cite journal | vauthors = Logan RP, Walker MM | title = ABC of the upper gastrointestinal tract: Epidemiology and diagnosis of Helicobacter pylori infection | journal = BMJ | volume = 323 | issue = 7318 | pages = 920–2 | date = October 2001 | pmid = 11668141 | pmc = 1121445 | doi = 10.1136/bmj.323.7318.920 }}</ref> Generally, repeating endoscopy is not recommended to confirm ''H. pylori'' eradication, unless there are specific indications to repeat the procedure.<ref name="Crowe 2019" />

==Transmission==
''Helicobacter pylori'' is contagious, and is [[pathogen transmission|transmitted]] through direct contact either with [[saliva]] (oral-oral) or [[feces]] ([[fecal–oral route]]), but mainly through the oral–oral route.<ref name="de Brito"/> Consistent with these transmission routes, the bacteria have been isolated from [[feces]], [[saliva]], and [[dental plaque]].<ref name="Reshetnyak">{{cite journal |vauthors=Reshetnyak VI, Burmistrov AI, Maev IV |title=Helicobacter pylori: Commensal, symbiont or pathogen? |journal=World J Gastroenterol |volume=27 |issue=7 |pages=545–560 |date=February 2021 |pmid=33642828 |pmc=7901052 |doi=10.3748/wjg.v27.i7.545 |doi-access=free |url=}}</ref> ''H.&nbsp;pylori'' may also be transmitted by consuming contaminated food or water.<ref name="Rahat" /> Transmission occurs mainly within families in developed nations, but also from the broader community in developing countries.<ref name="pmid17382274">{{cite journal | vauthors = Delport W, van der Merwe SW | title = The transmission of Helicobacter pylori: the effects of analysis method and study population on inference | journal = Best Practice & Research. Clinical Gastroenterology | volume = 21 | issue = 2 | pages = 215–36 | year = 2007 | pmid = 17382274 | doi = 10.1016/j.bpg.2006.10.001 | hdl = 2263/4083 | hdl-access = free }}</ref>

==Prevention==
To prevent the development of ''H. pylori''-related diseases when infection is suspected, antibiotic-based therapy regimens are recommended to [[Helicobacter pylori eradication protocols|eradicate the bacteria]].<ref name="medscape2024" /> When successful the disease progression is halted. First line therapy is recommended if low-grade gastric MALT lymphoma is diagnosed, regardless of evidence of ''H. pylori''. However, if a severe condition of atrophic gastritis with gastric lesions is reached antibiotic-based treatment regimens are not advised since such lesions are often not reversible and will progress to gastric cancer.<ref name="medscape2024"/> If the cancer is managed to be treated it is advised that an eradication program be followed to prevent a recurrence of infection, or reduce a recurrence of the cancer, known as metachronous.<ref name= "medscape2024" /><ref name= "pmid28771198">{{cite journal | vauthors = Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X | title = Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond | journal = International Journal of Molecular Sciences | volume = 18 | issue = 8 | pages = 1699 | date = August 2017 | pmid = 28771198 | pmc = 5578089 | doi = 10.3390/ijms18081699 | doi-access = free }}</ref><ref name="pmid31737682">{{cite journal | vauthors = Li L, Yu C | title = Helicobacter pylori Infection following Endoscopic Resection of Early Gastric Cancer | journal = BioMed Research International | volume = 2019  | year = 2019 | pages = 1–6 | pmid = 31737682 | pmc = 6816031 | doi = 10.1155/2019/9824964 | doi-access = free }}</ref>
  
Due to ''H.&nbsp;pylori''{{'s}} role as a major cause of certain diseases (particularly cancers) and its consistently increasing [[antibiotic resistance|resistance to antibiotic therapy]], there is an obvious need for alternative treatments.<ref name= "WJG" /> A vaccine targeted towards the development of gastric cancer, including MALT lymphoma, would also prevent the development of gastric ulcers.<ref name="FitzGerald" /> A vaccine that would be prophylactic for use in children, and one that would be therapeutic later are the main goals. Challenges to this are the extreme genomic diversity shown by ''H. pylori'' and complex host-immune responses.<ref name="WJG">{{cite journal |vauthors=Talebi Bezmin Abadi A |title= Vaccine against Helicobacter pylori: Inevitable approach |journal=World J Gastroenterol |volume=22 |issue=11 |pages=3150–7 |date=March 2016 |pmid=27003991 |pmc= 4789989 |doi=10.3748/wjg.v22.i11.3150 |doi-access=free |url=}}</ref><ref name=Blanchard2010>{{cite book | vauthors = Blanchard TG, Nedrud JG | veditors = Sutton P, Mitchell H | title = ''Helicobacter pylori'' in the 21st Century | chapter-url = https://books.google.com/books?id=RJuS0yre0W8C&pg=PA167 | access-date = 7 August 2013 | year = 2010 | publisher = CABI | isbn = 978-1-84593-594-8 | pages = 167–189 | chapter = 9. ''Helicobacter pylori'' Vaccines }}</ref>

Previous studies in the Netherlands and in the US have shown that such a prophylactic vaccine programme would be ultimately cost-effective.<ref name= deVries2009>{{cite journal | vauthors = de Vries R, Klok RM, Brouwers JR, Postma MJ | title = Cost-effectiveness of a potential future Helicobacter pylori vaccine in the Netherlands: the impact of varying the discount rate for health | journal = Vaccine | volume = 27 | issue = 6 | pages = 846–52 | date = February 2009 | pmid = 19084566 | doi = 10.1016/j.vaccine.2008.11.081 | url = http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?AccessionNumber=22009100732 | access-date = 7 August 2013 | archive-date = 10 May 2021 | archive-url = https://web.archive.org/web/20210510024012/https://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?AccessionNumber=22009100732 | url-status = live }}</ref><ref name="pmid19751153">{{cite journal | vauthors = Rupnow MF, Chang AH, Shachter RD, Owens DK, Parsonnet J | title = Cost-effectiveness of a potential prophylactic Helicobacter pylori vaccine in the United States | journal = The Journal of Infectious Diseases | volume = 200 | issue = 8 | pages = 1311–7 | date = October 2009 | pmid = 19751153 | doi = 10.1086/605845 | doi-access = free }}</ref> However, as of late 2019 there have been no advanced vaccine candidates and only one vaccine in a Phase I clinical trial.  Furthermore, development of a vaccine against ''H.&nbsp;pylori'' has not been a priority of major pharmaceutical companies.<ref name="Sutton2019">{{cite journal | vauthors = Sutton P, Boag JM | title = Status of vaccine research and development for Helicobacter pylori | journal = Vaccine | volume = 37 | issue = 50 | pages = 7295–7299 | date = November 2019 | pmid = 29627231 | pmc = 6892279 | doi = 10.1016/j.vaccine.2018.01.001 }}</ref> A key target for potential therapy is the [[proton-gated urea channel]], since the secretion of urease enables the survival of the bacterium.<ref name="RCSB2013">{{cite web |title=PDB101: Molecule of the Month: Proton-Gated Urea Channel |url=https://pdb101.rcsb.org/motm/158 |website=RCSB: PDB-101 |access-date=6 November 2023 |archive-date=6 November 2023 |archive-url=https://web.archive.org/web/20231106081513/https://pdb101.rcsb.org/motm/158 |url-status=live }}</ref>

==Treatment==
{{Further|Helicobacter pylori eradication protocols}}

The 2022 Maastricht Consensus Report recognised ''H. pylori'' gastritis as ''Helicobacter pylori induced gastritis'', and has been included in [[ICD11]].<ref name="Maastricht 2022">{{cite journal |vauthors=Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM |title=Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report |journal=Gut |volume= 71|issue= 9|pages= 1724–1762|date=August 2022 |pmid=35944925 |doi=10.1136/gutjnl-2022-327745 |url=|hdl=10486/714546 |hdl-access=free }}</ref><ref name="ICD11">{{cite web |title=ICD-11 for Mortality and Morbidity Statistics |url=https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f88597691 |website=icd.who.int |access-date=9 January 2024 |archive-date=15 October 2023 |archive-url=https://web.archive.org/web/20231015122454/https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f88597691 |url-status=live }}</ref><ref name="medscape2024">{{cite web |title=The Changes Made in the New Expert Consensus on H pylori |url=https://www.medscape.com/viewarticle/984066?&icd=login_success_email_match_fpf#vp_1 |website=Medscape |access-date=9 January 2024 |language=en |archive-date=9 January 2024 |archive-url=https://web.archive.org/web/20240109103649/https://www.medscape.com/viewarticle/984066?&icd=login_success_email_match_fpf#vp_1 |url-status=live }}</ref> Initially the infection tends to be superficial, localised to the upper mucosal layers of the stomach.<ref name="Azer">{{cite journal | title = Gastritis | journal = StatPearls | year = 2019 | pmid = 31334970 | last1 = Azer | first1 = S. A. | last2 = Akhondi | first2 = H. }}</ref> The intensity of chronic inflammation is related to the cytotoxicity of the ''H. pylori'' strain. A greater cytotoxicity will result in the change from a non-atrophic gastritis to an atrophic gastritis, with the loss of [[mucous gland]]s. This condition is a prequel to the development of peptic ulcers and gastric adenocarcinoma.<ref name="Azer"/>

Eradication of ''H. pylori'' is recommended to treat the infection, including when advanced to [[peptic ulcer disease]].  The recommendations for first-line treatment is a quadruple therapy consisting of a [[proton-pump inhibitor]], [[amoxicillin]], [[clarithromycin]], and [[metronidazole]]. Prior to treatment, testing is recommended to identify any pre-existing antibiotic resistances. A high rate of resistance to metronidazole has been observed. In areas of known clarithromycin resistance, the first-line therapy is changed to a [[Bismuth subcitrate|bismuth]] based regimen including [[tetracycline]] and metronidazole for 14 days. If one of these courses of treatment fails, it is suggested to use the alternative.<ref name="Maastricht 2022" />

Treatment failure may typically be attributed to antibiotic resistance, or inadequate acid suppression from proton-pump inhibitors.<ref name="Shirley" /> Following clinical trials, the use of the [[potassium-competitive acid blocker]] [[vonoprazan]], which has a greater acid suppressive action, was approved for use in the US in 2022.<ref>{{cite web |date=2022-05-04 |title=Two New Regimens Win FDA Approval for H. Pylori Infection |url=https://www.medpagetoday.com/gastroenterology/generalgastroenterology/98547 |access-date=2023-03-25 |website=www.medpagetoday.com |language=en |archive-date=25 March 2023 |archive-url=https://web.archive.org/web/20230325001109/https://www.medpagetoday.com/gastroenterology/generalgastroenterology/98547 |url-status=live }}</ref><ref name="Shirley">{{cite journal |vauthors=Shirley M |title=Vonoprazan: A Review in Helicobacter pylori Infection |journal=Drugs |volume=84 |issue=3 |pages=319–327 |date=March 2024 |pmid=38388872 |pmc=11090951 |doi=10.1007/s40265-023-01991-5 |url=}}</ref> Its recommended use is in combination with amoxicillin, with or without clarithromycin. It has been shown to have a faster action and can be used with or without food.<ref name="Shirley" /> Successful eradication regimens have revolutionised the treatment of peptic ulcers.<ref name="pmid1971318">{{cite journal | vauthors = Rauws EA, Tytgat GN | title = Cure of duodenal ulcer associated with eradication of Helicobacter pylori | journal = Lancet | volume = 335 | issue = 8700 | pages = 1233–5 | date = May 1990 | pmid = 1971318 | doi = 10.1016/0140-6736(90)91301-P | s2cid = 41888935 }}</ref><ref name="pmid28151409">{{cite journal | vauthors = Burkitt MD, Duckworth CA, Williams JM, Pritchard DM | title = Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models | journal = Disease Models & Mechanisms | volume = 10 | issue = 2 | pages = 89–104 | date = February 2017 | pmid = 28151409 | pmc = 5312008 | doi = 10.1242/dmm.027649 }}</ref> Eradication of ''H. pylori'' is also associated with a subsequent decreased risk of duodenal or gastric ulcer recurrence.<ref name="Crowe 2019" />

[[Plant extract]]s and [[probiotic]] foods are being increasingly used as [[Combination therapy|add-ons]] to usual treatments. Probiotic yogurts containing [[lactic acid bacteria]] ''[[Bifidobacteria]]'' and ''[[Lactobacillus]]'' exert a suppressive effect on ''H.&nbsp;pylori'' infection, and their use has been shown to improve the rates of eradication.<ref name="Violeta" /> Some commensal intestinal bacteria as part of the [[gut microbiota]] produce [[butyrate]] that acts as a [[Prebiotic (nutrition)|prebiotic]] and enhances the mucosal immune barrier. Their use as probiotics may help balance the gut dysbiosis that accompanies antibiotic use.<ref name="Zhu">{{cite journal |vauthors=Zhu LB, Zhang YC, Huang HH, Lin J |title=Prospects for clinical applications of butyrate-producing bacteria |journal=World J Clin Pediatr |volume=10 |issue=5 |pages=84–92 |date=September 2021 |pmid=34616650 |pmc=8465514 |doi=10.5409/wjcp.v10.i5.84 |doi-access=free |url=}}</ref> Some probiotic strains have been shown to have bactericidal and bacteriostatic activity against ''H. pylori'', and also help to balance the gut dysbiosis.<ref name="Saraceno">{{cite journal |vauthors=Saracino IM, Pavoni M, Saccomanno L, Fiorini G, Pesci V, Foschi C, Piccirilli G, Bernardini G, Holton J, Figura N, Lazzarotto T, Borghi C, Vaira B |title=Antimicrobial Efficacy of Five Probiotic Strains Against Helicobacter pylori |journal=Antibiotics |volume=9 |issue=5 |date=May 2020 |page=244 |pmid=32403331 |pmc=7277513 |doi=10.3390/antibiotics9050244 |doi-access=free |url=}}</ref><ref name="Shadvar">{{cite journal |last1=Shadvar |first1=Neda |last2=Akrami |first2=Sousan |last3=Mousavi Sagharchi |first3=Seyyed-Mohammad-Amin |last4=Askandar |first4=Rafee Habib |last5=Merati |first5=Alireza |last6=Aghayari |first6=Masoomeh |last7=Kaviani |first7=Nikki |last8=Afkhami |first8=Hamed |last9=Kashfi |first9=Mojtaba |title=A review for non-antibiotic treatment of Helicobacter pylori: new insight |journal=Frontiers in Microbiology |date=7 May 2024 |volume=15 |doi=10.3389/fmicb.2024.1379209 |doi-access=free |pmid=38774508 |pmc=11106852 |language=English |issn=1664-302X}}</ref> Antibiotics have a negative impact on gastrointestinal microbiota and cause nausea, diarrhea, and [[Emesis|sickness]] for which probiotics can alleviate.<ref name="Shadvar"/>

=== Antibiotic resistance ===
Increasing [[antibiotic resistance]] is the main cause of initial treatment failure. Factors linked to resistance include mutations, [[efflux pump]]s, and the formation of [[biofilm]]s.<ref name="Soto">{{cite journal |vauthors=Soto SM |title=Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm |journal=Virulence |volume=4 |issue=3 |pages=223–9 |date=April 2013 |pmid=23380871 |pmc=3711980 |doi=10.4161/viru.23724 |url=}}</ref><ref name="Cai">{{cite journal |last1=Cai |first1=Yuying |last2=Wang |first2=Caixia |last3=Chen |first3=Zhenghong |last4=Xu |first4=Zhengzheng |last5=Li |first5=Huanjie |last6=Li |first6=Wenjuan |last7=Sun |first7=Yundong |title=Transporters HP0939, HP0497, and HP0471 participate in intrinsic multidrug resistance and biofilm formation in Helicobacter pylori by enhancing drug efflux |url=https://onlinelibrary.wiley.com/doi/10.1111/hel.12715 |journal=Helicobacter |access-date=15 February 2024 |language=en |doi=10.1111/hel.12715 |date=August 2020 |volume=25 |issue=4 |pages=e12715 |pmid=32548895 |s2cid=219726485 |archive-date=15 February 2024 |archive-url=https://web.archive.org/web/20240215084607/https://onlinelibrary.wiley.com/doi/10.1111/hel.12715 |url-status=live }}</ref> One of the main [[antibiotic]]s used in eradication therapies is [[clarithromycin]], but clarithromycin-resistant strains have become well-established and the use of alternative antibiotics needs to be considered. Fortunately, non-invasive stool tests for clarithromycin have become available that allow selection of patients that are likely to respond to the therapy.<ref>{{cite journal | vauthors = Mommersteeg MC, Nieuwenburg SA, Wolters LM, Roovers BH, van Vuuren HA, Verhaar AP, Bruno MJ, Kuipers EJ, Peppelenbosch MP, Spaander MC, Fuhler GM | title =  The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance. | journal =  United European Gastroenterol J | volume = 11 | issue = 9 | pages = e894-903| date = November 2023 | pmid = 37854002 | pmc = 10637120 | doi = 10.1002/ueg2.12473 | doi-access = free}}</ref> Multidrug resistance has also increased.<ref name="Cai"/> Additional rounds of antibiotics or other therapies may be used.<ref name="Stenström B, Mendis A, Marshall B 2008 608–12">{{cite journal | vauthors = Stenström B, Mendis A, Marshall B | title = Helicobacter pylori--the latest in diagnosis and treatment | journal = Australian Family Physician | volume = 37 | issue = 8 | pages = 608–12 | date = August 2008 | pmid = 18704207 }}</ref><ref>{{cite journal | vauthors = Fischbach L, Evans EL | title = Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori | journal = Alimentary Pharmacology & Therapeutics | volume = 26 | issue = 3 | pages = 343–57 | date = August 2007 | pmid = 17635369 | doi = 10.1111/j.1365-2036.2007.03386.x | s2cid = 20973127 | type = Meta-analysis }}</ref><ref>{{cite journal | vauthors = Graham DY, Shiotani A | title = New concepts of resistance in the treatment of Helicobacter pylori infections | journal = Nature Clinical Practice. Gastroenterology & Hepatology | volume = 5 | issue = 6 | pages = 321–31 | date = June 2008 | pmid = 18446147 | pmc = 2841357 | doi = 10.1038/ncpgasthep1138 }}</ref> [[Next generation sequencing]] is looked to for identifying initial specific antibiotic resistances that will help in targeting more effective treatment.<ref name="Pohl">{{cite journal |vauthors=Pohl D, Keller PM, Bordier V, Wagner K |title=Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing |journal=World J Gastroenterol |volume=25 |issue=32 |pages=4629–4660 |date=August 2019 |pmid=31528091 |pmc=6718044 |doi=10.3748/wjg.v25.i32.4629 |doi-access=free |url=}}</ref>

In 2018, the [[WHO]] listed ''H. pylori'' as a high priority pathogen for the research and [[Drug discovery|discovery of new drugs]] and treatments.<ref name="Sukri">{{cite journal |vauthors=Sukri A, Hanafiah A, Patil S, Lopes BS |title=The Potential of Alternative Therapies and Vaccine Candidates against Helicobacter pylori |journal=Pharmaceuticals |volume=16 |issue=4 |date=April 2023 |page=552 |pmid=37111309 |pmc=10141204 |doi=10.3390/ph16040552 |doi-access=free |url=}}</ref> The increasing antibiotic resistance encountered has spurred interest in developing alternative therapies using a number of plant compounds.<ref name="Vaou">{{cite journal |vauthors=Vaou N, Stavropoulou E, Voidarou C, Tsigalou C, Bezirtzoglou E |title=Towards Advances in Medicinal Plant Antimicrobial Activity: A Review Study on Challenges and Future Perspectives |journal=Microorganisms |volume=9 |issue=10 |date=September 2021 |page=2041 |pmid=34683362 |pmc=8541629 |doi=10.3390/microorganisms9102041 |doi-access=free }}</ref><ref name="pmid20459098">{{cite journal | vauthors = Moon JK, Kim JR, Ahn YJ, Shibamoto T | title = Analysis and anti-Helicobacter activity of sulforaphane and related compounds present in broccoli ( Brassica oleracea L.) sprouts | journal = Journal of Agricultural and Food Chemistry | volume = 58 | issue = 11 | pages = 6672–7 | date = June 2010 | pmid = 20459098 | doi = 10.1021/jf1003573 | bibcode = 2010JAFC...58.6672M }}</ref> Plant compounds have fewer side effects than synthetic drugs. Most plant extracts contain a complex mix of components that may not act on their own as antimicrobials but can work together with antibiotics to enhance treatment and work towards overcoming resistance.<ref name="Vaou"/> Plant compounds have a different mechanism of action that has proved useful in fighting antimicrobial resistance. For example, various compounds can act by inhibiting enzymes such as urease, and weakening adhesions to the mucous membrane.<ref name="Sathianarayanan">{{cite journal |vauthors=Sathianarayanan S, Ammanath AV, Biswas R, B A, Sukumaran S, Venkidasamy B |title=A new approach against Helicobacter pylori using plants and its constituents: A review study |journal=Microb Pathog |volume=168 |issue= |pages=105594 |date=July 2022 |pmid=35605740 |doi=10.1016/j.micpath.2022.105594 |s2cid=248975163 |url=}}</ref> Sulfur-containing compounds from plants with high concentrations of polysulfides, [[coumarin]]s, and [[terpene]]s have all been shown to be effective against ''H. pylori''.<ref name="Vaou"/>

''H. pylori'' is found in saliva and [[dental plaque]]. Its transmission is known to include oral-oral, suggesting that the dental plaque biofilm may act as a reservoir for the bacteria. Periodontal therapy or [[scaling and root planing]] has therefore been suggested as an additional treatment to enhance eradication rates, but more research is needed.<ref name="Rahat">{{cite journal |vauthors=Rahat M, Saqib M, Ahmed M, Suleman M, Ismail SM, Mumtaz H, Khalid H |title=Use of eradication therapy in adjunction to periodontal therapy versus alone for treatment of Helicobacter pylori infections: a mini review |journal=Ann Med Surg (Lond) |volume=85 |issue=6 |pages=2756–2760 |date=June 2023 |pmid=37363585 |pmc=10289787 |doi=10.1097/MS9.0000000000000741 |url=}}</ref><ref name="BMC2023">{{cite journal |vauthors=Moradi Y, Majidi L, Khateri S, Azh N, Gheshlagh RG, Saniee N, Zarei M, Moradpour F |title=The association between periodontal diseases and helicobacter pylori: an updated meta-analysis of observational studies |journal=BMC Oral Health |volume=23 |issue=1 |pages=523 |date=July 2023 |pmid=37496045 |pmc=10369707 |doi=10.1186/s12903-023-03232-3 |doi-access=free |url=}}</ref>

=== Cancers ===
{{Further|Carcinogenesis#Bacterial}}

==== Stomach cancer ====
{{Main|Stomach cancer#Management}}
''Helicobacter pylori'' is a risk factor for [[gastric adenocarcinoma]]s.<ref name="Smyth">{{cite journal |vauthors=Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F |title=Gastric cancer |journal=Lancet |volume=396 |issue=10251 |pages=635–648 |date=August 2020 |pmid=32861308 |doi=10.1016/S0140-6736(20)31288-5 |url=}}</ref> Treatment is highly aggressive, with even localized disease being treated sequentially with chemotherapy and radiotherapy before surgical resection.<ref name="pmid28810883">{{cite journal | vauthors = Badgwell B, Das P, Ajani J | title = Treatment of localized gastric and gastroesophageal adenocarcinoma: the role of accurate staging and preoperative therapy | journal = Journal of Hematology & Oncology | volume = 10 | issue = 1 | pages = 149 | date = August 2017 | pmid = 28810883 | pmc = 5558742 | doi = 10.1186/s13045-017-0517-9 | doi-access = free }}</ref> Since this cancer, once developed, is independent of ''H.&nbsp;pylori'' infection, eradication regimens are not used.<ref name="Laird-Fick">{{cite journal|vauthors=Laird-Fick HS, Saini S, Hillard JR|date=August 2016|title=Gastric adenocarcinoma: the role of Helicobacter pylori in pathogenesis and prevention efforts|journal=Postgraduate Medical Journal|volume=92|issue=1090|pages=471–7|doi=10.1136/postgradmedj-2016-133997|pmid=27222587|s2cid=20739020}}</ref>

==== Gastric MALT lymphoma and DLBCL====
{{Main|MALT lymphoma#Treatment}}
[[MALT lymphoma]]s are [[Malignancy|malignancies]] of [[mucosa-associated lymphoid tissue]]. Early gastric MALTomas due to ''H. pylori'' may be successfully treated (70–95% of cases) with one or more [[Helicobacter pylori eradication protocols|eradication programs]].<ref name="Violeta"/> Some 50–80% of patients who experience eradication of the pathogen develop a remission and long-term clinical control of their lymphoma within 3–28&nbsp;months. [[Radiation therapy]] to the stomach and surrounding (i.e. peri-gastric) lymph nodes has also been used to successfully treat these localized cases. Patients with non-localized (i.e. systemic Ann Arbor stage&nbsp;III and IV) disease who are free of symptoms have been treated with [[watchful waiting]] or, if symptomatic, with the [[immunotherapy]] drug [[rituximab]] (given for 4&nbsp;weeks) combined with the [[chemotherapy]] drug [[chlorambucil]] for 6–12&nbsp;months; 58% of these patients attain a 58% progression-free survival rate at 5&nbsp;years. Frail stage III/IV patients have been successfully treated with rituximab or the chemotherapy drug [[cyclophosphamide]] alone.<ref name="pmid31246587">{{cite journal | vauthors = Bron D, Meuleman N | title = Marginal zone lymphomas: second most common lymphomas in older patients | journal = Current Opinion in Oncology | volume = 31 | issue = 5 | pages = 386–393 | date = September 2019 | pmid = 31246587 | doi = 10.1097/CCO.0000000000000554 | s2cid = 195765608 }}</ref> Antibiotic-proton pump inhibitor eradication therapy and localized radiation therapy have been used successfully to treat H.&nbsp;pylori-positive MALT lymphomas of the rectum; however radiation therapy has given slightly better results and therefore been suggested to be the disease's preferred treatment.<ref name="pmid17570523">{{cite journal | vauthors = Kobayashi T, Takahashi N, Hagiwara Y, Tamaru J, Kayano H, Jin-nai I, Bessho M, Niitsu N | title = Successful radiotherapy in a patient with primary rectal mucosa-associated lymphoid tissue lymphoma without the API2-MALT1 fusion gene: a case report and review of the literature | journal = Leukemia Research | volume = 32 | issue = 1 | pages = 173–5 | date = January 2008 | pmid = 17570523 | doi = 10.1016/j.leukres.2007.04.017 }}</ref> However, the generally recognized treatment of choice for patients with systemic involvement uses various chemotherapy drugs often combined with rituximab.

A MALT lymphoma may rarely transform into a more aggressive [[diffuse large B-cell lymphoma]] (DLBCL).<ref name="Matysiak">{{cite journal |vauthors=Matysiak-Budnik T, Priadko K, Bossard C, Chapelle N, Ruskoné-Fourmestraux A |title=Clinical Management of Patients with Gastric MALT Lymphoma: A Gastroenterologist's Point of View |journal=Cancers |volume=15 |issue=15 |date=July 2023 |page=3811 |pmid=37568627 |pmc=10417821 |doi=10.3390/cancers15153811 |doi-access=free |url=}}</ref> Where this is associated with ''H. pylori'' infection, the DLBCL is less aggressive and more amenable to treatment.<ref name="pmid28288708">{{cite journal | vauthors = Casulo C, Friedberg J | title = Transformation of marginal zone lymphoma (and association with other lymphomas) | journal = Best Practice & Research. Clinical Haematology | volume = 30 | issue = 1–2 | pages = 131–138 | year = 2017 | pmid = 28288708 | doi = 10.1016/j.beha.2016.08.029 }}</ref><ref name="pmid24949857">{{cite journal | vauthors = Kuo SH, Yeh KH, Chen LT, Lin CW, Hsu PN, Hsu C, Wu MS, Tzeng YS, Tsai HJ, Wang HP, Cheng AL | title = Helicobacter pylori-related diffuse large B-cell lymphoma of the stomach: a distinct entity with lower aggressiveness and higher chemosensitivity | journal = Blood Cancer Journal | volume = 4 | issue = 6 | pages = e220 | date = June 2014 | pmid = 24949857 | pmc = 4080211 | doi = 10.1038/bcj.2014.40 }}</ref><ref name="pmid31455250">{{cite journal | vauthors = Cheng Y, Xiao Y, Zhou R, Liao Y, Zhou J, Ma X | title = Prognostic significance of helicobacter pylori-infection in gastric diffuse large B-cell lymphoma | journal = BMC Cancer | volume = 19 | issue = 1 | pages = 842 | date = August 2019 | pmid = 31455250 | pmc = 6712724 | doi = 10.1186/s12885-019-6067-5 | doi-access = free }}</ref> When limited to the stomach, they have sometimes been successfully treated with ''H. pylori'' eradication programs.<ref name="pmid25852262"/><ref name="pmid24949857"/><ref name="pmid31727764">{{cite journal | vauthors = Tsai HJ, Tai JJ, Chen LT, Wu MS, Yeh KH, Lin CW, Wang TE, Wang HP, Yu FJ, Liou JM, Hsiao CF, Cheng TY, Yeh HJ, Ko CW, Chen MJ, Lo GH, Hsu PI, Chang CS, Hwang WS, Chuang SS, Lee HW, Shun CT, Chiu CF, Wang WM, Hsieh CY, Liu TW, Lin JT, Kuo SH, Cheng AL | title = A multicenter prospective study of first-line antibiotic therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma with histological evidence of mucosa-associated lymphoid tissue | journal = Haematologica | volume = 105 | issue = 7 | pages = e349–e354 | date = July 2020 | pmid = 31727764 | doi = 10.3324/haematol.2019.228775 | pmc = 7327622 | doi-access = free }}</ref><ref name="pmid31455250"/> If unresponsive or showing a deterioration, a more conventional chemotherapy ([[CHOP (chemotherapy)|CHOP]]), immunotherapy, or local radiotherapy can be considered, and any of these or a combination have successfully treated these more advanced types.<ref name="pmid24949857"/><ref name="pmid31455250"/>

==Prognosis==
''Helicobacter pylori'' colonizes the stomach for decades in most people, and induces chronic gastritis, a long-lasting inflammation of the stomach. In most 
cases symptoms are never experienced but about 10–20% of those infected will ultimately develop gastric and duodenal ulcers, and have a possible 1–2% lifetime risk of gastric cancer.<ref name="Debowski"/>

''H. pylori'' thrives in a high salt diet, which is seen as an environmental risk factor for its association with gastric cancer. A diet high in salt enhances colonization, increases inflammation, increases the expression of ''H. pylori'' virulence factors, and intensifies chronic gastritis.<ref name="Balendra">{{cite journal |vauthors=Balendra V, Amoroso C, Galassi B, Esposto J, Bareggi C, Luu J, Scaramella L, Ghidini M |title=High-Salt Diet Exacerbates H. pylori Infection and Increases Gastric Cancer Risks |journal=J Pers Med |volume=13 |issue=9 |date=August 2023 |page=1325 |pmid=37763093 |pmc=10533117 |doi=10.3390/jpm13091325 |doi-access=free }}</ref><ref name="Jaroenlapnopparat">{{cite journal |vauthors=Jaroenlapnopparat A, Bhatia K, Coban S |title=Inflammation and Gastric Cancer |journal=Diseases |volume=10 |issue=3 |date=June 2022 |page=35 |pmid=35892729 |pmc=9326573 |doi=10.3390/diseases10030035 |doi-access=free }}</ref> Paradoxically, extracts of [[kimchi]], a salted probiotic food, has been found to have a preventive effect on ''H. pylori''–associated gastric [[carcinogenesis]].<ref name="Park2021">{{cite journal |vauthors=Park JM, Han YM, Oh JY, Lee DY, Choi SH, Hahm KB |title=Transcriptome profiling implicated in beneficiary actions of kimchi extracts against Helicobacter pylori infection |journal=J Clin Biochem Nutr |volume=69 |issue=2 |pages=171–187 |date=September 2021 |pmid=34616109 |pmc=8482382 |doi=10.3164/jcbn.20-116 |url=}}</ref>

In the absence of treatment, ''H.&nbsp;pylori'' infection usually persists for life.<ref name="Brown">{{cite journal | vauthors = Brown LM | title = Helicobacter pylori: epidemiology and routes of transmission | journal = Epidemiologic Reviews | volume = 22 | issue = 2 | pages = 283–97 | year = 2000 | pmid = 11218379 | doi = 10.1093/oxfordjournals.epirev.a018040 | doi-access = free }}</ref> Infection may disappear in the elderly as the stomach's mucosa becomes increasingly atrophic and inhospitable to colonization. Some studies in young children up to two years of age have shown that infection can be transient in this age group.<ref name="Pacifico">{{cite journal |vauthors=Pacifico L, Osborn JF, Bonci E, Romaggioli S, Baldini R, Chiesa C |title=Probiotics for the treatment of Helicobacter pylori infection in children |journal=World J Gastroenterol |volume=20 |issue=3 |pages=673–83 |date=January 2014 |pmid=24574741 |pmc=3921477 |doi=10.3748/wjg.v20.i3.673 |doi-access=free |url=}}</ref><ref name=Goodman_2005>{{cite journal | vauthors = Goodman KJ, O'rourke K, Day RS, Wang C, Nurgalieva Z, Phillips CV, Aragaki C, Campos A, de la Rosa JM | title = Dynamics of Helicobacter pylori infection in a US-Mexico cohort during the first two years of life | journal = International Journal of Epidemiology | volume = 34 | issue = 6 | pages = 1348–55 | date = December 2005 | pmid = 16076858 | doi = 10.1093/ije/dyi152 | doi-access = free }}</ref>

It is possible for ''H.&nbsp;pylori'' to re-establish in a person after eradication. This recurrence can be caused by the original strain ([[recrudescence]]), or be caused by a different strain (reinfection). A 2017 meta-analysis showed that the global per-person annual rates of recurrence, reinfection, and recrudescence is 4.3%, 3.1%, and 2.2% respectively. It is unclear what the main risk factors are.<ref>{{cite journal |last1=Li |first1=R |last2=Zhang |first2=P |last3=Hu |first3=Z |last4=Yi |first4=Y |last5=Chen |first5=L |last6=Zhang |first6=H |title=Helicobacter pylori reinfection and its risk factors after initial eradication: A protocol for systematic review and meta-analysis. |journal=Medicine |date=14 May 2021 |volume=100 |issue=19 |pages=e25949 |doi=10.1097/MD.0000000000025949 |pmid=34106668 |pmc=8133036 |doi-access=free}}</ref>

Mounting evidence suggests ''H.&nbsp;pylori'' has an important role in protection from some diseases.<ref name="WJG2020"/> The incidence of [[gastroesophageal reflux disease|acid reflux disease]], [[Barrett's esophagus]], and [[esophageal cancer]] have been rising dramatically at the same time as ''H.&nbsp;pylori''{{'}}s presence decreases.<ref name = Blaser_2005 /> In 1996, [[Martin J. Blaser]] advanced the hypothesis that ''H.&nbsp;pylori'' has a beneficial effect by regulating the acidity of the stomach contents.<ref name="pmid14755326"/><ref name = Blaser_2005/> The hypothesis is not universally accepted, as several [[randomized controlled trials]] failed to demonstrate worsening of acid reflux disease symptoms following eradication of ''H.&nbsp;pylori''.<ref name="Graham 2007">{{cite journal | vauthors = Graham DY, Yamaoka Y, Malaty HM | title = Contemplating the future without Helicobacter pylori and the dire consequences hypothesis | journal = Helicobacter | volume = 12 | issue = Suppl 2 | pages = 64–8 | date = November 2007 | pmid = 17991179 | pmc = 3128250 | doi = 10.1111/j.1523-5378.2007.00566.x }}</ref><ref name="Delaney 2005">{{cite journal | vauthors = Delaney B, McColl K | title = Review article: Helicobacter pylori and gastro-oesophageal reflux disease | journal = Alimentary Pharmacology & Therapeutics | volume = 22 | issue = Suppl 1 | pages = 32–40 | date = August 2005 | pmid = 16042657 | doi = 10.1111/j.1365-2036.2005.02607.x | s2cid = 34921548 | type = Review }}</ref> Nevertheless, Blaser has reasserted his view that ''H.&nbsp;pylori'' is a member of the normal [[gastric microbiota]].<ref name="Blaser 2006">{{cite journal | vauthors = Blaser MJ | title = Who are we? Indigenous microbes and the ecology of human diseases | journal = EMBO Reports | volume = 7 | issue = 10 | pages = 956–60 | date = October 2006 | pmid = 17016449 | pmc = 1618379 | doi = 10.1038/sj.embor.7400812 }}</ref> He postulates that the changes in gastric physiology caused by the loss of ''H.&nbsp;pylori'' account for the recent increase in incidence of several diseases, including [[type 2 diabetes]], [[obesity]], and asthma.<ref name="Blaser 2006"/><ref name="Blaser 2008">{{cite journal | vauthors = Blaser MJ, Chen Y, Reibman J | title = Does Helicobacter pylori protect against asthma and allergy? | journal = Gut | volume = 57 | issue = 5 | pages = 561–7 | date = May 2008 | pmid = 18194986 | pmc = 3888205 | doi = 10.1136/gut.2007.133462 }}</ref> His group has recently shown that ''H.&nbsp;pylori'' colonization is associated with a lower [[incidence (epidemiology)|incidence]] of childhood asthma.<ref>{{cite journal | vauthors = Chen Y, Blaser MJ | title = Helicobacter pylori colonization is inversely associated with childhood asthma | journal = The Journal of Infectious Diseases | volume = 198 | issue = 4 | pages = 553–60 | date = August 2008 | pmid = 18598192 | pmc = 3902975 | doi = 10.1086/590158 }}</ref>

==Epidemiology==
In 2023, it was estimated that about two-thirds of the world's population were infected with ''H.&nbsp;pylori'' infection, being more common in [[developing countries]].<ref name="CDC2024" /> ''H. pylori'' infection is more prevalent in South America, Sub-Saharan Africa, and the Middle East.<ref name="pmid28151409"/> The global prevalence declined markedly in the decade following 2010, with a particular reduction in Africa.<ref name=Li2023>{{cite journal |doi=10.1016/S2468-1253(23)00070-5 |title=Global prevalence of Helicobacter pylori infection between 1980 and 2022: a systematic review and meta-analysis |journal=The Lancet Gastroenterology & Hepatology |date=19 April 2023 |vauthors= Li Y, Choi H, Leung K, Jiang F, Graham DY, Leung WK|volume=8 |issue=6 |pages=553–564 |pmid=37086739 |s2cid=258272798 }}</ref>

The age when someone acquires this bacterium seems to influence the pathologic outcome of the infection. People infected at an early age are likely to develop more intense inflammation that may be followed by atrophic gastritis with a higher subsequent risk of gastric ulcer, gastric cancer, or both. Acquisition at an older age brings different gastric changes more likely to lead to duodenal ulcer.<ref name="Brown"/> Infections are usually acquired in early childhood in all countries.<ref name="Kusters2006"/> However, the infection rate of children in developing nations is higher than in [[Developed country|industrialized nations]], probably due to poor sanitary conditions, perhaps combined with lower antibiotics usage for unrelated pathologies. In developed nations, it is currently uncommon to find infected children, but the percentage of infected people increases with age. The higher prevalence among the elderly reflects higher infection rates incurred in childhood.<ref name="Kusters2006"/> In the United States, prevalence appears higher in [[African American|African-American]] and [[Hispanic and Latino Americans|Hispanic]] populations, most likely due to socioeconomic factors.<ref>{{cite journal | vauthors = Smoak BL, Kelley PW, Taylor DN | title = Seroprevalence of Helicobacter pylori infections in a cohort of US Army recruits | journal = American Journal of Epidemiology | volume = 139 | issue = 5 | pages = 513–9 | date = March 1994 | pmid = 8154475 | doi = 10.1093/oxfordjournals.aje.a117034 }}</ref><ref>{{cite journal | vauthors = Everhart JE, Kruszon-Moran D, Perez-Perez GI, Tralka TS, McQuillan G | title = Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States | journal = The Journal of Infectious Diseases | volume = 181 | issue = 4 | pages = 1359–63 | date = April 2000 | pmid = 10762567 | doi = 10.1086/315384 | doi-access = free }}</ref> The lower rate of infection in the West is largely attributed to higher hygiene standards and widespread use of antibiotics. Despite high rates of infection in certain areas of the world, the overall frequency of ''H.&nbsp;pylori'' infection is declining.<ref name="pmid17382273">{{cite journal | vauthors = Malaty HM | title = Epidemiology of Helicobacter pylori infection | journal = Best Practice & Research. Clinical Gastroenterology | volume = 21 | issue = 2 | pages = 205–14 | year = 2007 | pmid = 17382273 | doi = 10.1016/j.bpg.2006.10.005 }}</ref> However, antibiotic resistance is appearing in ''H.&nbsp;pylori''; many metronidazole- and clarithromycin-resistant strains are found in most parts of the world.<ref>{{cite journal | vauthors = Mégraud F | title = H pylori antibiotic resistance: prevalence, importance, and advances in testing | journal = Gut | volume = 53 | issue = 9 | pages = 1374–84 | date = September 2004 | pmid = 15306603 | pmc = 1774187 | doi = 10.1136/gut.2003.022111 }}</ref>

==History==
{{See also|Timeline of peptic ulcer disease and Helicobacter pylori}}''Helicobacter pylori'' [[Recent African origin of modern humans|migrated out of Africa]] along with its human host around 60,000&nbsp;years ago.<ref name=Correa2012>{{cite journal | vauthors = Correa P, Piazuelo MB | title = Evolutionary History of the Helicobacter pylori Genome: Implications for Gastric Carcinogenesis | journal = Gut and Liver | volume = 6 | issue = 1 | pages = 21–8 | date = January 2012 | pmid = 22375167 | pmc = 3286735 | doi = 10.5009/gnl.2012.6.1.21 |doi-access=free}}
</ref> Research has shown that [[genetic diversity]] in ''H.&nbsp;pylori'', like that of its host, decreases with geographic distance from [[Eastern Africa|East Africa]]. Using the genetic diversity data, researchers have created simulations that indicate the bacteria seem to have spread from East Africa around 58,000&nbsp;years ago. Their results indicate modern humans were already infected by ''H.&nbsp;pylori'' before their migrations out of Africa, and it has remained associated with human hosts since that time.<ref>{{cite journal | vauthors = Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, Falush D, Stamer C, Prugnolle F, van der Merwe SW, Yamaoka Y, Graham DY, Perez-Trallero E, Wadstrom T, Suerbaum S, Achtman M | title = An African origin for the intimate association between humans and Helicobacter pylori | journal = Nature | volume = 445 | issue = 7130 | pages = 915–918 | date = February 2007 | pmid = 17287725 | pmc = 1847463 | doi = 10.1038/nature05562 | bibcode = 2007Natur.445..915L }}</ref>

''H.&nbsp;pylori'' was first discovered in the stomachs of patients with gastritis and [[ulcers]] in 1982 by [[Barry Marshall]] and [[Robin Warren]] of [[Perth, Western Australia]]. At the time, the conventional thinking was that no bacterium could live in the acid environment of the human stomach. In recognition of their discovery, Marshall and Warren were awarded the 2005&nbsp;[[Nobel Prize in Physiology or Medicine]].<ref>{{cite web |url=https://www.nobelprize.org/prizes/medicine/2005/summary/ |title=The Nobel Prize in Physiology or Medicine 2005 |access-date=30 August 2018 |archive-date=23 May 2020 |archive-url=https://web.archive.org/web/20200523072638/https://www.nobelprize.org/prizes/medicine/2005/summary/ |url-status=live }}</ref>

Before the research of Marshall and Warren, German scientists found spiral-shaped [[bacteria]] in the lining of the human stomach in 1875, but they were unable to [[Microbiological culture|culture]] them, and the results were eventually forgotten.<ref name=Blaser_2005>{{cite journal | vauthors = Blaser MJ | title = An endangered species in the stomach | journal = Scientific American | volume = 292 | issue = 2 | pages = 38–45 | date = February 2005 | pmid = 15715390 | doi = 10.1038/scientificamerican0205-38 | bibcode = 2005SciAm.292b..38B }}</ref> The Italian researcher [[Giulio Bizzozero]] described similarly shaped bacteria living in the acidic environment of the stomach of dogs in 1893.<ref>{{cite journal |vauthors=Bizzozero G |s2cid=85338121 |author-link=Giulio Bizzozero |year=1893 |title=Ueber die schlauchförmigen Drüsen des Magendarmkanals und die Beziehungen ihres Epitheles zu dem Oberflächenepithel der Schleimhaut |journal=Archiv für Mikroskopische Anatomie |volume=42 |pages=82–152 |doi=10.1007/BF02975307 |url=https://zenodo.org/record/1702379 |access-date=29 June 2019 |archive-date=2 December 2020 |archive-url=https://web.archive.org/web/20201202011115/https://zenodo.org/record/1702379 |url-status=live }}</ref> Professor [[Walery Jaworski]] of the [[Jagiellonian University]] in [[Kraków]] investigated sediments of gastric washings obtained by [[Gastric lavage|lavage]] from humans in 1899. Among some rod-like bacteria, he also found bacteria with a characteristic spiral shape, which he called ''Vibrio rugula''. He was the first to suggest a possible role of this organism in the pathogenesis of gastric diseases. His work was included in the ''Handbook of Gastric Diseases'', but it had little impact, as it was published only in Polish.<ref>{{cite journal | vauthors = Konturek JW | title = Discovery by Jaworski of Helicobacter pylori and its pathogenetic role in peptic ulcer, gastritis and gastric cancer | journal = Journal of Physiology and Pharmacology | volume = 54 | issue = Suppl 3 | pages = 23–41 | date = December 2003 | pmid = 15075463 | url = http://www.jpp.krakow.pl/journal/archive/1203_s3/pdf/23_1203_s3_article.pdf | access-date = 25 August 2008 | archive-url = https://web.archive.org/web/20040930111720/http://www.jpp.krakow.pl/journal/archive/1203_s3/pdf/23_1203_s3_article.pdf | archive-date = 30 September 2004 }}</ref> Several small studies conducted in the early 20th century demonstrated the presence of curved rods in the stomachs of many people with peptic ulcers and stomach cancers.<ref name="Egan 2007">{{cite journal | vauthors = Egan BJ, O'Morain CA | title = A historical perspective of Helicobacter gastroduodenitis and its complications | journal = Best Practice & Research. Clinical Gastroenterology | volume = 21 | issue = 2 | pages = 335–46 | year = 2007 | pmid = 17382281 | doi = 10.1016/j.bpg.2006.12.002 }}</ref> Interest in the bacteria waned, however, when an American study published in 1954 failed to observe the bacteria in 1180 stomach biopsies.<ref name="Palmer 1954">{{cite journal | vauthors = Palmer ED | title = Investigation of the gastric mucosa spirochetes of the human | journal = Gastroenterology | volume = 27 | issue = 2 | pages = 218–20 | date = August 1954 | pmid = 13183283 | doi = 10.1016/S0016-5085(19)36173-6 }}</ref>

Interest in understanding the role of bacteria in stomach diseases was rekindled in the 1970s, with the visualization of bacteria in the stomachs of people with gastric ulcers.<ref name="Steer 1975">{{cite journal | vauthors = Steer HW | title = Ultrastructure of cell migration {{sic|thro|ught|nolink=y}} the gastric epithelium and its relationship to bacteria | journal = Journal of Clinical Pathology | volume = 28 | issue = 8 | pages = 639–46 | date = August 1975 | pmid = 1184762 | pmc = 475793 | doi = 10.1136/jcp.28.8.639 }}</ref> The bacteria had also been observed in 1979, by Robin Warren, who researched it further with Barry Marshall from 1981. After unsuccessful attempts at culturing the bacteria from the stomach, they finally succeeded in visualizing colonies in 1982, when they unintentionally left their [[Petri dishes]] incubating for five days over the [[Easter]] weekend. In their original paper, Warren and Marshall contended that most stomach ulcers and gastritis were caused by bacterial infection and not by [[stress (medicine)|stress]] or [[Spice|spicy food]], as had been assumed before.<ref name="Unidentified curved bacilli in the">{{cite journal | vauthors = Marshall BJ, Warren JR | title = Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration | journal = Lancet | volume = 1 | issue = 8390 | pages = 1311–5 | date = June 1984 | pmid = 6145023 | doi = 10.1016/S0140-6736(84)91816-6 | s2cid = 10066001 }}</ref>

Some skepticism was expressed initially, but within a few years multiple research groups had verified the association of ''H.&nbsp;pylori'' with gastritis and, to a lesser extent, ulcers.<ref>{{cite web |url=http://www.csicop.org/si/show/bacteria_ulcers_and_ostracism_h._pylori_and_the_making_of_a_myth/ |title=Bacteria, Ulcers, and Ostracism? ''H.&nbsp;pylori'' and the making of a myth |year=2004 |last=Atwood |first=K.C. IV |access-date=2 August 2008 |archive-date=5 November 2009 |archive-url=https://web.archive.org/web/20091105131647/http://www.csicop.org/si/show/bacteria_ulcers_and_ostracism_h._pylori_and_the_making_of_a_myth |url-status=live }}</ref> To demonstrate ''H.&nbsp;pylori'' caused gastritis and was not merely a bystander, Marshall drank a beaker of ''H.&nbsp;pylori'' culture. He became ill with nausea and vomiting several days later. An endoscopy 10&nbsp;days after inoculation revealed signs of gastritis and the presence of ''H.&nbsp;pylori''. These results suggested ''H.&nbsp;pylori'' was the causative agent. Marshall and Warren went on to demonstrate antibiotics are effective in the treatment of many cases of gastritis. In 1994, the [[National Institutes of Health]] stated most recurrent duodenal and gastric ulcers were caused by ''H.&nbsp;pylori'', and recommended antibiotics be included in the treatment regimen.<ref>{{cite report |title=''Helicobacter pylori'' in peptic ulcer disease |series=NIH Consensus Statement Online |date=7–9 January 1994 |volume=12 |issue=1 |pages=1–23 |access-date=21 December 2004 |url=http://consensus.nih.gov/1994/1994HelicobacterPyloriUlcer094html.htm |archive-date=19 August 2011 |archive-url=https://web.archive.org/web/20110819144041/http://consensus.nih.gov/1994/1994HelicobacterPyloriUlcer094html.htm |url-status=dead }}</ref>

The bacterium was initially named ''Campylobacter pyloridis'', then renamed ''C.&nbsp;pylori'' in 1987 (''pylori'' being the [[genitive]] of ''[[pylorus]]'', the circular opening leading from the stomach into the duodenum, from the [[Ancient Greek]] word ''πυλωρός'', which means [[gatekeeper]]<ref name=Liddell1980/>).<ref>{{cite journal |vauthors=Marshall BS, Goodwin CS |title=Revised nomenclature of ''Campylobacter pyloridis'' |journal=International Journal of Systematic Bacteriology |volume=37 |issue=1 |year=1987 |pages = 68 |doi=10.1099/00207713-37-1-68|doi-access=free }}</ref> When [[16S ribosomal RNA]] [[DNA sequencing|gene sequencing]] and other research showed in 1989 that the bacterium did not belong in the genus ''[[Campylobacter]]'', it was placed in its own [[genus]], ''Helicobacter'' from the Ancient Greek ''έλιξ'' (''hělix'') "spiral" or "coil".<ref name=Liddell1980>{{cite book |author1-link=Henry George Liddell |last1=Liddell |first1=Henry G. |author2-link=Robert Scott (philologist) |last2=Scott |first2=Robert |title=A Lexicon: Abridged from Liddell and Scott's Greek-English Lexicon |publisher=Oxford University Press |place=Oxford, UK |year=1966 |isbn=978-0-19-910207-5 |url-access=registration |url=https://archive.org/details/lexicon00lidd}}</ref><ref>{{cite journal |vauthors=Goodwin CS, Armstrong JA, Chilvers T, Peters M, Collins MD, Sly L, McConnell W, Harper WE |title=Transfer of ''Campylobacter pylori'' and ''Campylobacter mustelae'' to ''Helicobacter'' gen. nov. as ''Helicobacter pylori'' comb. nov. and ''Helicobacter mustelae'' comb. nov. respectively |journal=International Journal of Systematic Bacteriology |volume=39 |issue=4 |year=1989 |pages=397–405 |doi=10.1099/00207713-39-4-397|doi-access=free }}</ref>

In October 1987, a group of experts met in Copenhagen to found the European Helicobacter Study Group (EHSG), an international multidisciplinary research group and the only institution focused on ''H.&nbsp;pylori''.<ref>{{cite journal | vauthors = Buckley MJ, O'Morain CA | title = Helicobacter biology--discovery | journal = British Medical Bulletin | volume = 54 | issue = 1 | pages = 7–16 | year = 1998 | pmid = 9604426 | doi = 10.1093/oxfordjournals.bmb.a011681 | doi-access = free }}</ref> The Group is involved with the Annual International Workshop on Helicobacter and Related Bacteria,<ref>{{cite journal | vauthors = Mégraud F | title = Evolution of Helicobacter pylori research as observed through the workshops of the European Helicobacter Study Group | journal = Helicobacter | volume = 12 Suppl 2 | issue = Suppl&nbsp;2 | pages = 1–5 | date = November 2007 | pmid = 17991169 | doi = 10.1111/j.1523-5378.2007.00581.x | s2cid = 45841196 | collaboration = European Helicobacter Study Group }}</ref> (renamed as the European Helicobacter and Microbiota Study Group<ref name="EHMSG">{{cite web |title=EHMSG |url=https://www.ehmsg.org/ |website=Ehmsg2019 |access-date=11 January 2024 |language=en |archive-date=11 January 2024 |archive-url=https://web.archive.org/web/20240111084024/https://www.ehmsg.org/ |url-status=live }}</ref>), the Maastricht Consensus Reports (European Consensus on the management of ''H.&nbsp;pylori''),<ref name="Report 2012">{{cite journal | vauthors = Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ | title = Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report | journal = Gut | volume = 61 | issue = 5 | pages = 646–64 | date = May 2012 | pmid = 22491499 | doi = 10.1136/gutjnl-2012-302084 | url = http://gut.bmj.com/content/61/5/646.long | s2cid = 1401974 | collaboration = European Helicobacter Study Group | doi-access = free | hdl = 1765/64813 | hdl-access = free | access-date = 7 December 2012 | archive-date = 4 July 2021 | archive-url = https://web.archive.org/web/20210704233427/https://gut.bmj.com/content/61/5/646.long | url-status = live }}</ref><ref name=Maastricht_2_Consensus_Report>{{cite journal | vauthors = Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ | title = Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report | journal = Gut | volume = 56 | issue = 6 | pages = 772–81 | date = June 2007 | pmid = 17170018 | pmc = 1954853 | doi = 10.1136/gut.2006.101634 }}</ref><ref>{{cite journal | vauthors = Malfertheiner P, Mégraud F, O'Morain C, Hungin AP, Jones R, Axon A, Graham DY, Tytgat G | title = Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report | journal = Alimentary Pharmacology & Therapeutics | volume = 16 | issue = 2 | pages = 167–80 | date = February 2002 | pmid = 11860399 | doi = 10.1046/j.1365-2036.2002.01169.x | collaboration = European Helicobacter Pylori Study Group (EHPSG) | s2cid = 6166458 }}</ref><ref>{{cite journal | vauthors = Malfertheiner P, Mégraud F, O'Morain C, Bell D, Bianchi Porro G, Deltenre M, Forman D, Gasbarrini G, Jaup B, Misiewicz JJ, Pajares J, Quina M, Rauws E | title = Current European concepts in the management of Helicobacter pylori infection--the Maastricht Consensus Report. The European Helicobacter Pylori Study Group (EHPSG) | journal = European Journal of Gastroenterology & Hepatology | volume = 9 | issue = 1 | pages = 1–2 | date = January 1997 | pmid = 9031888 | doi = 10.1097/00042737-199701000-00002 | collaboration = European Helicobacter Pylori Study Group (EHPSG) | s2cid = 36930542 }}</ref> and other educational and research projects, including two international long-term projects:
* European Registry on ''H.&nbsp;pylori'' Management (Hp-EuReg) – a database systematically registering the routine clinical practice of European gastroenterologists.<ref>{{cite journal |vauthors=McNicholl AG, Gasbarrini A, Tepes B |display-authors=etal |title=Pan-European registry on ''H.&nbsp;pylori'' management (Hp-EuReg): Interim analysis of 5,792&nbsp;patients |journal=Helicobacter |date=September 2014 |volume=2014 |pages = 69}}</ref>
* Optimal ''H.&nbsp;pylori'' management in primary care (OptiCare) – a long-term educational project aiming to disseminate the evidence based recommendations of the Maastricht&nbsp;IV Consensus to primary care physicians in Europe, funded by an educational grant from [[United European Gastroenterology]].<ref>{{cite web |url=https://www.ueg.eu/education/courses/online-courses/helicobacter-pylori/ |title=Management of ''Helicobacter pylori'' infection |series=Online courses |publisher=[[United European Gastroenterology]] |archive-url=https://web.archive.org/web/20150402195040/https://www.ueg.eu/education/courses/online-courses/helicobacter-pylori/ |archive-date=2 April 2015}}</ref><ref>{{cite web |url=https://www.ueg.eu/fileadmin/ueg/UEG.AnnualReport.2012/page31.html |title=Annual Report 2012 |publisher=[[United European Gastroenterology]] |access-date=25 February 2015 |archive-date=4 June 2016 |archive-url=https://web.archive.org/web/20160604212022/https://www.ueg.eu/fileadmin/ueg/UEG.AnnualReport.2012/page31.html |url-status=dead }}</ref>

== Research ==
Results from ''[[in vitro]]'' studies suggest that [[fatty acid]]s, mainly [[PUFA|polyunsaturated fatty acids]], have a bactericidal effect against ''H.&nbsp;pylori'', but their ''[[in vivo]]'' effects have not been proven.<ref name=JungLee2016>{{cite journal | vauthors = Jung SW, Lee SW | title = The antibacterial effect of fatty acids on Helicobacter pylori infection | journal = The Korean Journal of Internal Medicine | volume = 31 | issue = 1 | pages = 30–5 | date = January 2016 | pmid = 26767854 | pmc = 4712431 | doi = 10.3904/kjim.2016.31.1.30 | type = Review }}</ref>

The antibiotic resistance provided by biofilms has generated much research into targeting the mechanisms of [[quorum sensing]] used in the formation of biofilms.<ref name="Zafer" />

A suitable vaccine for ''H. pylori'', either prophylactic or therapeutic, is an ongoing research aim.<ref name="de Brito"/> The [[Murdoch Children's Research Institute]] is working at developing a vaccine that instead of specifically targeting the bacteria, aims to inhibit the inflammation caused that leads to the associated diseases.<ref name="Sutton2019"/>

[[Gastric organoid]]s can be used as models for the study of ''H. pylori'' pathogenesis.<ref name="Doohan"/>

== See also ==
* [[List of oncogenic bacteria]]
* [[Infectious causes of cancer]]
* [[CagZ]]

== References ==
{{Reflist}}

== External links ==
{{Spoken Wikipedia|HelicobacterPylori.ogg|date=2009-02-24}}
{{Wikispecies}}
{{Commons category|Helicobacter pylori}}
* {{cite web |url=http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0015937 |archive-date=2013-06-13 |archive-url=https://web.archive.org/web/20130613122121/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0015937/ |title=Information on tests for ''H.&nbsp;pylori'' |date=29 August 2011 |department=[[National Institutes of Health]] |publisher=U.S. Department of Health and Human Services}}
* {{cite web |url=http://www.helicobacter.org |title=European Helicobacter Study Group (EHSG)}}
* {{cite web |url=https://bacdive.dsmz.de/index.php?search=6102&submit=Search |title=Type strain of ''Helicobacter pylori'' at Bac''Dive'' |website=Bacterial Diversity Metadatabase}}
* {{cite web |url=https://www.genome.jp/kegg-bin/show_organism?org=hpy |series=KEGG |website=Genome |place=Japan |title=Helicobacter pylori |id=26695}}

{{Medical resources
 | DiseasesDB      = 5702
 | ICD11           = {{ICD11|XN3DY}}, {{ICD11|DA42.1}}, {{ICD11|DA51.0}}, {{ICD11|DA60.1}}, {{ICD11|DA60.2}}, {{ICD11|DA62.1}}, {{ICD11|DA63.1}}, {{ICD11|DA63.2}}
 | ICD10           = {{ICD10|B98.0}}
 | ICD9            = {{ICD9|041.86}}
 | ICDO            =
 | OMIM            =600263
 | MedlinePlus     = 000229
 | eMedicineSubj   = med
 | eMedicineTopic  = 962
 | eMedicine_mult  =
 | MeshID          = D016481
 | Scholia         = Q180556
}}
{{Gram-negative bacterial diseases}}
{{Taxonbar|from=Q180556}}
{{Authority control}}

{{DEFAULTSORT:Helicobacter Pylori}}
[[Category:Helicobacter pylori| ]]
[[Category:Bacteria described in 1989]]
[[Category:Conditions diagnosed by stool test]]
[[Category:Infectious causes of cancer]]
[[Category:Pathogenic bacteria]]