Editing Ulcerative colitis (section)

==Pathophysiology==
{{Pathophysiology in CD vs. UC}}

An increased amount of colonic sulfate-reducing bacteria has been observed in some people with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide. Human colonic mucosa is maintained by the colonic epithelial barrier and immune cells in the lamina propria (see [[intestinal mucosal barrier]]). The [[short-chain fatty acid]] ''n''-butyrate gets oxidized through the [[beta oxidation]] pathway into carbon dioxide and ketone bodies. It has been shown that ''n''-butyrate helps supply nutrients to this epithelial barrier. Studies have proposed that hydrogen sulfide plays a role in impairing this beta-oxidation pathway by interrupting the short chain acetyl-CoA dehydrogenase, an enzyme within the pathway. Furthermore, it has been suggested that the protective effect of smoking in ulcerative colitis is due to the [[hydrogen cyanide]] from cigarette smoke reacting with hydrogen sulfide to produce the non-toxic isothiocyanate, thereby inhibiting sulfides from interrupting the pathway.<ref name=Levine>{{cite journal | vauthors = Levine J, Ellis CJ, Furne JK, Springfield J, Levitt MD | title = Fecal hydrogen sulfide production in ulcerative colitis | journal = The American Journal of Gastroenterology | volume = 93 | issue = 1 | pages = 83–87 | date = January 1998 | doi = 10.1111/j.1572-0241.1998.083_c.x | pmid = 9448181 | s2cid = 3141574 | df = dmy-all }}</ref> An unrelated study suggested that the sulfur contained in red meats and alcohol may lead to an increased risk of relapse for people in remission.<ref name=Roediger/>

Other proposed mechanisms driving the pathophysiology of ulcerative colitis involve an abnormal immune response to the normal [[gut microbiota]]. This involves abnormal activity of [[antigen presenting cells]] (APCs) including [[dendritic cells]] and [[macrophages]]. Normally, dendritic cells and macrophages patrol the intestinal epithelium and [[phagocytose]] (engulf and destroy) pathogenic microorganisms and present parts of the microorganism as [[antigens]] to [[T-cells]] to stimulate differentiation and activation of the T-cells.<ref name="Gros 2023">{{cite journal |last1=Gros |first1=Beatriz |last2=Kaplan |first2=Gilaad G. |title=Ulcerative Colitis in Adults: A Review |journal=JAMA |date=12 September 2023 |volume=330 |issue=10 |pages=951–965 |doi=10.1001/jama.2023.15389|pmid=37698559 |s2cid=261696018 }}</ref> However, in ulcerative colitis, aberrant activity of dendritic cells and macrophages results in them phagocytosing bacteria of the normal gut microbiome. After ingesting the microbiome bacterium, the APCs release the cytokine [[TNFα]] which stimulates inflammatory signaling and recruits inflammatory cells to the intestines, leading to the inflammation that is characteristic of ulcerative colitis.<ref name="Gros 2023" /> The TNF inhibitors, including [[infliximab]], [[adalimumab]] and [[golimumab]], are used to inhibit this step during the treatment of ulcerative colitis.<ref name="Gros 2023" /> After phagocytosing the microbe, the APCs then enter the [[superior mesenteric lymph node|mesenteric lymph nodes]] where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines [[interleukin 12|IL-12]] and [[interleukin-23|IL-23]] which lead to T cell differentiation into [[helper T cell|Th1]] and [[Th17]] T-cells.<ref name="Gros 2023" /> IL-12 and IL-23 signaling is blocked by the biologic [[ustekinumab]] and IL-23 is blocked by [[guselkumab]], [[mirikizumab]] and [[risankizumab]], medications that are used in the treatment of ulcerative colitis.<ref name="Gros 2023" /> From the mesenteric lymph node, the T-cells then enter the intestinal lymphatic venule which provides transport to the intestinal epithelium where they mediate further inflammation characteristic of ulcerative colitis.<ref name="Gros 2023" /> The T-cells exit the lymphatic venule via the adhesion protein mucosal vascular addressin cell adhesion molecule 1 [[MAdCAM-1]], the ulcerative colitis biologic treatment [[vedolizumab]] inhibits T-cell migration out of the lymphatic venules by blocking binding to MAdCAM-1.<ref name="Gros 2023" /> While the medications [[ozanimod]] and [[etrasimod]] inhibit the [[sphingosine-1-phosphate receptor]] to prevent T-cell migration into the efferent lymphatic venules.<ref name="Gros 2023" /> Once the mature Th1 and Th17 T-cells exit the efferent lymphatic venule, they travel to the intestinal mucosa and cause further inflammation. T-cell mediated inflammation is thought to be driven by the [[JAK-STAT]] intracellular T-cell signaling pathway, leading to the [[transcription (biology)|transcription]], [[translation (biology)|translation]] and release of inflammatory cytokines. This T-cell JAK-STAT signaling is inhibited by the medications [[tofacitinib]], [[filgotinib]] and [[upadacitinib]] which are used in the treatment of ulcerative colitis.<ref name="Gros 2023" />