Editing Ulcerative colitis (section)

==Causes==
{{Risk factors in CD vs. UC}}
Ulcerative colitis is an [[autoimmune disease]] characterized by [[T-cells]] infiltrating the colon.<ref name="Targeting Improves MSC Treatment of Inflammatory Bowel Disease">{{cite journal | vauthors = Ko IK, Kim BG, Awadallah A, Mikulan J, Lin P, Letterio JJ, Dennis JE | title = Targeting improves MSC treatment of inflammatory bowel disease | journal = Molecular Therapy | volume = 18 | issue = 7 | pages = 1365–1372 | date = July 2010 | pmid = 20389289 | pmc = 2911249 | doi = 10.1038/mt.2010.54 }}</ref> No direct causes for UC are known, but factors such as genetics, environment, and an overactive immune system play a role.<ref name=NIH2014>{{cite web|title=Ulcerative Colitis|url=https://www.niddk.nih.gov/health-information/digestive-diseases/ulcerative-colitis|website=NIDDK|access-date=3 August 2016|date=September 2014}}</ref> UC is associated with comorbidities that produce symptoms in many areas of the body outside the digestive system.

===Genetic factors===
A genetic component to the cause of UC can be hypothesized based on aggregation of UC in families, variation of prevalence between different ethnicities, [[genetic marker]]s and [[Genetic linkage|linkages]].<ref name=Orholm>{{cite journal | vauthors = Orholm M, Binder V, Sørensen TI, Rasmussen LP, Kyvik KO | title = Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study | journal = Scandinavian Journal of Gastroenterology | volume = 35 | issue = 10 | pages = 1075–1081 | date = October 2000 | pmid = 11099061 | doi = 10.1080/003655200451207 | s2cid = 218907577 }}</ref> In addition, the identical [[twin studies|twin]] [[Concordance (genetics)|concordance]] rate is 10%, whereas the [[dizygotic twin]] concordance rate is only 3%.<ref name=Orholm /><ref>{{cite journal | vauthors = Tysk C, Lindberg E, Järnerot G, Flodérus-Myrhed B | title = Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking | journal = Gut | volume = 29 | issue = 7 | pages = 990–996 | date = July 1988 | pmid = 3396969 | pmc = 1433769 | doi = 10.1136/gut.29.7.990 }}</ref> Between 8 and 14% of people with ulcerative colitis have a family history of inflammatory bowel disease.<ref name=Ungaro /> In addition, people with a first degree relative with UC have a four-fold increase in their risk of developing the disease.<ref name=Ungaro />

Twelve regions of the [[genome]] may be linked to UC, including, in the order of their discovery, chromosomes 16, 12, 6, 14, 5, 19, 1, and 3,<ref name=Baumgart/> but none of these [[Locus (genetics)|loci]] has been consistently shown to be at fault, suggesting that the disorder is influenced by multiple genes. For example, chromosome band 1p36 is one such region thought to be linked to inflammatory bowel disease.<ref>{{cite journal | vauthors = Cho JH, Nicolae DL, Ramos R, Fields CT, Rabenau K, Corradino S, Brant SR, Espinosa R, LeBeau M, Hanauer SB, Bodzin J, Bonen DK | title = Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease | journal = Human Molecular Genetics | volume = 9 | issue = 9 | pages = 1425–1432 | date = May 2000 | pmid = 10814724 | doi = 10.1093/hmg/9.9.1425 | doi-access = free }}</ref> Some of the putative regions encode transporter proteins such as [[OCTN1]] and [[OCTN2]]. Other potential regions involve cell scaffolding proteins such as the [[Membrane-associated guanylate kinase|MAGUK family]]. [[Human leukocyte antigen]] associations may even be at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.<ref name=Baumgart/>

Multiple autoimmune disorders are associated with ulcerative colitis, including [[celiac disease]],<ref name=Shah_Celiac>{{cite journal | vauthors = Shah A, Walker M, Burger D, Martin N, von Wulffen M, Koloski N, Jones M, Talley NJ, Holtmann GJ | title = Link Between Celiac Disease and Inflammatory Bowel Disease | journal = Journal of Clinical Gastroenterology | volume = 53 | issue = 7 | pages = 514–522 | date = August 2019 | pmid = 29762265 | doi = 10.1097/MCG.0000000000001033 | s2cid = 44102071 }}</ref> [[psoriasis]],<ref>{{cite journal | vauthors = Fu Y, Lee CH, Chi CC | title = Association of Psoriasis With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis | journal = JAMA Dermatology | volume = 154 | issue = 12 | pages = 1417–1423 | date = December 2018 | pmid = 30422277 | pmc = 6583370 | doi = 10.1001/jamadermatol.2018.3631 }}</ref> [[lupus erythematosus]],<ref>{{cite journal | vauthors = Katsanos KH, Voulgari PV, Tsianos EV | title = Inflammatory bowel disease and lupus: a systematic review of the literature | journal = Journal of Crohn's & Colitis | volume = 6 | issue = 7 | pages = 735–742 | date = August 2012 | pmid = 22504032 | doi = 10.1016/j.crohns.2012.03.005 | doi-access = free }}</ref> [[rheumatoid arthritis]],<ref name=Chen_RA>{{cite journal | vauthors = Chen Y, Chen L, Xing C, Deng G, Zeng F, Xie T, Gu L, Yang H | title = The risk of rheumatoid arthritis among patients with inflammatory bowel disease: a systematic review and meta-analysis | journal = BMC Gastroenterology | volume = 20 | issue = 1 | pages = 192 | date = June 2020 | pmid = 32552882 | pmc = 7301504 | doi = 10.1186/s12876-020-01339-3 | doi-access = free }}</ref> [[episcleritis]], and [[scleritis]].<ref name=Troncoso /> Ulcerative colitis is also associated with [[acute intermittent porphyria]].<ref>{{cite journal | vauthors = Sieg I, Beckh K, Kersten U, Doss MO | title = Manifestation of acute intermittent porphyria in patients with chronic inflammatory bowel disease | journal = Zeitschrift für Gastroenterologie | volume = 29 | issue = 11 | pages = 602–605 | date = November 1991 | pmid = 1771936 }}</ref>

===Environmental factors===
Many hypotheses have been raised for environmental factors contributing to the pathogenesis of ulcerative colitis, including [[Diet (nutrition)|diet]], [[breastfeeding]] and medications. Breastfeeding may have a protective effect in the development of ulcerative colitis.<ref name=Xu_Breastfeeding_UC>{{cite journal | vauthors = Xu L, Lochhead P, Ko Y, Claggett B, Leong RW, Ananthakrishnan AN | title = Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis | journal = Alimentary Pharmacology & Therapeutics | volume = 46 | issue = 9 | pages = 780–789 | date = November 2017 | pmid = 28892171 | pmc = 5688338 | doi = 10.1111/apt.14291 }}</ref><ref>{{cite journal | vauthors = Corrao G, Tragnone A, Caprilli R, Trallori G, Papi C, Andreoli A, Di Paolo M, Riegler G, Rigo GP, Ferraù O, Mansi C, Ingrosso M, Valpiani D | title = Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC) | journal = International Journal of Epidemiology | volume = 27 | issue = 3 | pages = 397–404 | date = June 1998 | pmid = 9698126 | doi = 10.1093/ije/27.3.397 | doi-access = free }}</ref> One study of [[isotretinoin]] found a small increase in the rate of UC.<ref>{{cite journal | vauthors = Wolverton SE, Harper JC | title = Important controversies associated with isotretinoin therapy for acne | journal = American Journal of Clinical Dermatology | volume = 14 | issue = 2 | pages = 71–76 | date = April 2013 | pmid = 23559397 | doi = 10.1007/s40257-013-0014-z | s2cid = 918753 }}</ref>

As the colon is exposed to many dietary substances which may encourage [[inflammation]], dietary factors have been hypothesized to play a role in the [[pathogenesis]] of both ulcerative colitis and Crohn's disease. However, research does not show a link between diet and the development of ulcerative colitis. Few studies have investigated such an association; one study showed no [[Association (statistics)|association]] of refined [[sugar]] on the number of people affected of ulcerative colitis.<ref>{{cite journal | vauthors = Järnerot G, Järnmark I, Nilsson K | title = Consumption of refined sugar by patients with Crohn's disease, ulcerative colitis, or irritable bowel syndrome | journal = Scandinavian Journal of Gastroenterology | volume = 18 | issue = 8 | pages = 999–1002 | date = November 1983 | pmid = 6673083 | doi = 10.3109/00365528309181832 }}</ref> High intake of [[unsaturated fat]] and [[vitamin B6]] may enhance the risk of developing ulcerative colitis.<ref name="Geerling 2000">{{cite journal | vauthors = Geerling BJ, Dagnelie PC, Badart-Smook A, Russel MG, Stockbrügger RW, Brummer RJ | title = Diet as a risk factor for the development of ulcerative colitis | journal = The American Journal of Gastroenterology | volume = 95 | issue = 4 | pages = 1008–1013 | date = April 2000 | doi = 10.1111/j.1572-0241.2000.01942.x | pmid = 10763951 | s2cid = 11295804 }}</ref> Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages.<ref name="Jowett 2004">{{cite journal | vauthors = Jowett SL, Seal CJ, Pearce MS, Phillips E, Gregory W, Barton JR, Welfare MR | title = Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study | journal = Gut | volume = 53 | issue = 10 | pages = 1479–1484 | date = October 2004 | pmid = 15361498 | pmc = 1774231 | doi = 10.1136/gut.2003.024828 }}</ref><ref name="Andersen 2012">{{cite journal | vauthors = Andersen V, Olsen A, Carbonnel F, Tjønneland A, Vogel U | title = Diet and risk of inflammatory bowel disease | journal = Digestive and Liver Disease | volume = 44 | issue = 3 | pages = 185–194 | date = March 2012 | pmid = 22055893 | doi = 10.1016/j.dld.2011.10.001 }}</ref> Specifically, sulfur has been investigated as being involved in the cause of ulcerative colitis, but this is controversial.<ref name="Tilg 2004">{{cite journal | vauthors = Tilg H, Kaser A | title = Diet and relapsing ulcerative colitis: take off the meat? | journal = Gut | volume = 53 | issue = 10 | pages = 1399–1401 | date = October 2004 | pmid = 15361484 | pmc = 1774255 | doi = 10.1136/gut.2003.035287 }}</ref> [[low-sulfur diet|Sulfur restricted diets]] have been investigated in people with UC and animal models of the disease. The theory of sulfur as an etiological factor is related to the [[gut microbiota]] and mucosal sulfide detoxification in addition to the diet.<ref name="Moore 1998">{{cite journal | vauthors = Moore J, Babidge W, Millard S, Roediger W | title = Colonic luminal hydrogen sulfide is not elevated in ulcerative colitis | journal = Digestive Diseases and Sciences | volume = 43 | issue = 1 | pages = 162–165 | date = January 1998 | pmid = 9508519 | doi = 10.1023/A:1018848709769 | s2cid = 20919357 }}</ref><ref name="Jørgensen 2001">{{cite journal | vauthors = Jørgensen J, Mortensen PB | title = Hydrogen sulfide and colonic epithelial metabolism: implications for ulcerative colitis | journal = Digestive Diseases and Sciences | volume = 46 | issue = 8 | pages = 1722–1732 | date = August 2001 | pmid = 11508674 | doi = 10.1023/A:1010661706385 | s2cid = 30373968 }}</ref><ref name="Picton 2007">{{cite journal | vauthors = Picton R, Eggo MC, Langman MJ, Singh S | title = Impaired detoxication of hydrogen sulfide in ulcerative colitis? | journal = Digestive Diseases and Sciences | volume = 52 | issue = 2 | pages = 373–378 | date = February 2007 | pmid = 17216575 | doi = 10.1007/s10620-006-9529-y | s2cid = 22547709 }}</ref>

As a result of [[Perfluorooctanoic acid#Robert Bilott investigation|a class-action lawsuit and community settlement]] with [[DuPont]], three [[Epidemiology|epidemiologists]] conducted studies on the population surrounding a chemical plant that was exposed to PFOA at levels greater than in the general population. The studies concluded that there was an association between [[Perfluorooctanoic acid|PFOA]] exposure and six health outcomes, one of which being ulcerative colitis.<ref>{{cite journal | last1 = Nicole | first1 = W. | title = PFOA and Cancer in a Highly Exposed Community: New Findings from the C8 Science Panel | doi = 10.1289/ehp.121-A340 | journal = Environmental Health Perspectives | volume = 121 | issue = 11–12 | pages = A340 | year = 2013 | pmid = 24284021| pmc = 3855507}}</ref>

===Alternative theories===
Levels of [[sulfate-reducing bacteria]] tend to be higher in persons with ulcerative colitis, which could indicate higher levels of [[hydrogen sulfide]] in the intestine. An alternative theory suggests that the symptoms of the disease may be caused by toxic effects of the hydrogen sulfide on the cells lining the intestine.<ref name=Roediger>{{cite journal | vauthors = Roediger WE, Moore J, Babidge W | title = Colonic sulfide in pathogenesis and treatment of ulcerative colitis | journal = Digestive Diseases and Sciences | volume = 42 | issue = 8 | pages = 1571–1579 | date = August 1997 | pmid = 9286219 | doi = 10.1023/A:1018851723920 | s2cid = 25496705 }}</ref>

Infection by ''[[Mycobacterium avium]]'', subspecies ''[[paratuberculosis]]'', has been proposed as the ultimate cause of both ulcerative colitis and Crohn's disease.<ref>{{cite journal | vauthors = Pierce ES | title = Could ''Mycobacterium avium'' subspecies ''paratuberculosis'' cause Crohn's disease, ulcerative colitis…and colorectal cancer? | journal = Infectious Agents and Cancer | volume = 13 | pages = 1 | date = 2018 | pmid = 29308085 | pmc = 5753485 | doi = 10.1186/s13027-017-0172-3 | doi-access = free }}</ref>
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