Colite | EPFL Graph Search

Colitis is swelling or inflammation of the large intestine (colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label colitis (without qualification) is used if: The cause of the inflammation in the colon is undetermined; for example, colitis may be applied to Crohn's disease at a time when the diagnosis is unknown, or The context is clear; for example, an individual with ulcerative colitis is talking about their disease with a physician who knows the diagnosis. The signs and symptoms of colitis are quite variable and dependent on the cause of the given colitis and factors that modify its course and severity. Common symptoms of colitis may include: mild to severe abdominal pains and tenderness (depending on the stage of the disease), persistent hemorrhagic diarrhea with pus either present or absent in the stools, fecal incontinence, flatulence, fatigue, loss of appetite and unexplained weight loss. More severe symptoms may include: shortness of breath, a fast or irregular heartbeat and fever. Other less common or rare non-specific symptoms that may accompany colitis include: arthritis, mouth ulcers, painful, red and swollen skin and irritated, bloodshot eyes. Signs seen on colonoscopy include: colonic mucosal erythema (redness of the colon's inner surface), ulcerations and hemorrhage. Symptoms suggestive of colitis are worked-up by obtaining the medical history, a physical examination and laboratory tests (CBC, electrolytes, stool culture and sensitivity, stool ova and parasites et cetera). Additional tests may include medical imaging (e.g. abdominal computed tomography, abdominal X-rays) and an examination with a camera inserted into the rectum (sigmoidoscopy, colonoscopy). An important investigation in the assessment of colitis is biopsy. A very small piece of tissue (usually about 2mm) is removed from the bowel mucosa during endoscopy and examined under the microscope by a histopathologist.

Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration

Kristina Schoonjans, Alessia Perino, Maroun Bou Sleiman, Giovanni Sorrentino, Ece Yildiz, Gaby El Alam

BACKGROUND & AIMS: Renewal and patterning of the intestinal epithelium is coordinated by intestinal stem cells (ISCs); dietary and metabolic factors provide signals to the niche that control ISC activity. Bile acids (BAs), metabolites in the gut, signal nutrient availability by activating the G protein-coupled bile acid receptor 1 (GPBAR1, also called TGR5). TGR5 is expressed in the intestinal epithelium, but it is not clear how its activation affects ISCs and regeneration of the intestinal epithelium. We studied the role of BAs and TGR5 in intestinal renewal, and regulation of ISC function in mice and intestinal organoids. METHODS: We derived intestinal organoids from wild-type mice and Tgr5(-/-) mice, incubated them with BAs or the TGR5 agonist INT-777, and monitored ISC function by morphologic analyses and colony-forming assays. We disrupted Tgr5 specifically in Lgr5-positive ISCs in mice (Tgr5ISC(-/-) mice) and analyzed ISC number, proliferation, and differentiation by flow cytometry, immunofluorescence, and organoid assays. Tgr5ISC(-/-) mice were given cholecystokinin; we measured the effects of BA release into the intestinal lumen and on cell renewal. We induced colitis in Tgr5ISC(-/-) mice by administration of dextran sulfate sodium; disease severity was determined based on body weight, colon length, and histopathology analysis of colon biopsies. RESULTS: BAs and TGR5 agonists promoted growth of intestinal organoids. Administration of cholecystokinin to mice resulted in acute release of BAs into the intestinal lumen and increased proliferation of the intestinal epithelium. BAs and Tgr5 expression in ISCs were required for homeostatic intestinal epithelial renewal and fatespecification, and for regeneration after colitis induction. Tgr5ISC(-/-) mice developed more severe colitis than mice without Tgr5 disruption in ISCs. ISCs incubated with INT-777 increased activation of yes-associated protein 1 (YAP1) and of its upstream regulator SRC. Inhibitors of YAP1 and SRC prevented organoid growth induced by TGR5 activation. CONCLUSIONS: BAs promote regeneration of the intestinal epithelium via activation of TGR5 in ISCs, resulting in activation of SRC and YAP and activation of their target genes. Release of endogenous BAs in the intestinal lumen is sufficient to promote ISC renewal and drives regeneration in response to injury.

2020

Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis

Johan Auwerx, Mehdi Karoui

BACKGROUND & AIMS: The peroxisome proliferator-activated receptor gamma (PPAR gamma) has been proposed as a key inhibitor of colitis through attenuation of nuclear factor kappa B (NF-kappa B) activity. In inflammatory bowel disease, activators of NF-kappa B, including the bacterial receptor toll-like receptor (TLR)4, are elevated. We aimed to determine the role of bacteria and their signaling effects on PPAR gamma regulation during inflammatory bowel disease (IBD). METHODS: TLR4-transfected Caco-2 cells, germ-free mice, and mice devoid of functional TLR4 (Lps(d)/Lps(d) mice) were assessed for their expression of PPAR gamma in colonic tissues in the presence or absence of bacteria. This nuclear receptor expression and the polymorphisms of gene also were assessed in patients with Crohn's disease (CD) and ulcerative colitis (UC), 2 inflammatory bowel diseases resulting from an abnormal immune response to bacterial antigens. RESULTS: TLR4-transfected Caco-2 cells showed that the TLR4 signaling pathway elevated PPAR gamma expression and a PPAR gamma-dependent reporter in an I kappa kappa beta dependent fashion. Murine and human intestinal flora induced PPAR gamma expression in colonic epithelial cells of control mice. PPAR gamma expression was significantly higher in the colon of control compared with Lps(d)/Lps(d) mice. Although PPAR gamma levels appeared normal in patients with CD and controls, UC patients displayed a reduced expression of PPAR gamma confined to colonic epithelial cells, without any mutation in the PPAR gamma gene. CONCLUSIONS: These data showed that the commensal intestinal flora affects the expression of PPAR gamma and that PPAR gamma expression is considerably impaired in patients with UC.

2003

Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration

Kristina Schoonjans, Alessia Perino, Maroun Bou Sleiman, Giovanni Sorrentino, Ece Yildiz, Gaby El Alam

2020