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Pathophysiology GI Pathophysiology 2016. 11. 01. Jaeyoung Chun, M.D. 1 IBD IBS IBD : inflammatory bowel disease IBS : irritable bowel syndrome Introduction : IBD • Inflammatory bowel disease (IBD) – Chronic relapsing inflammation of the digestive tract – Rare • Two major forms – Crohn’s disease (CD) – Ulcerative colitis (UC) IBD : CD vs. UC Superficial inflammation Involved in any part of the GI tract Associated with complications such as strictures, fistulas and abscesses At a higher risk of colorectal cancer Introduction : IBS • Irritable bowel syndrome (IBS) – Functional gastrointestinal disease – Very common – Change in bowel habits : diarrhea, constipation – Abdominal pain or discomfort relieved with bowel movement IBD IBS Incidence Rare 5~20 / 100,000 Very common 67 / 1,000 person years (20% prevalence) Peak age of onset 20-30 & 60-70 years NA Sex (male : female) 1:1 1:2 Symptoms Chronic relapsing GI symptoms (abdominal pain, bowel habit change, etc) Radiologic findings Abnormal Normal Histologic findings Chronic inflammation Normal Treatment Anti-inflammatory drugs Immunomodulatory drugs Steroids Biologic agents Dietary modification Probiotics Anti-spasmodics Anti-depressants Prognosis Lifelong disease Complications (stricture, perforation, infection, or colorectal cancer) Affect quality of life, but not life threatening Crohn’s Disease Ulcerative Colitis Gastroenterology 2012;142:46-54 Incidence of IBD in Korea 6.0 5.0 Incidence (/105) 4.2 4.0 UC 3.0 3.1 CD 2.0 1.0 0.0 06 07 08 09 10 11 12 Year of diagnosis Population-based Cohort in the Songpa-Kangdong District, Seoul, Korea, 1986-2005 Database from the Health Insurance and Review Agency, 2006-2012 Yang SK, Kim JS et al. Inflamm Bowel Dis 2008;14:542–549 Kim HJ et al. Inflamm Bowel Dis 2015;21:623-630 IBD - Etiology Inflamm Bowel Dis 2015;21:912–922 IBD – Genetics 163 IBD risk loci Ann Gastroenterol 2014;27:294-303 Gut Microbiome • We are more “bacteria” than “human” – 10x the No. of human cells – 150x the No. of human genome • Microbiome as “human organ” – Weighs ~1kg – Is more akin to immune system than liver Gut Microbiome: Implication for Clinical Practice • Disease associated with dysregulated gut microbiome – – – – – – – – DM Obesity Metabolic syndrome Stress/anxiety Heart disease Allergic disorders Cancer IBD & IBS IBD & Gut Microbiota • Evidence for role of microbiota in IBD – Patients with IBD have less diverse microbiome. – Antibiotics improve disease course in some IBD patients. – Animal models of IBD require presence of microbiota for inflammation. – Many genetic risk loci for IBD involve pathways for protection of host against gut microbiota. – Established association of diet, which impacts microbiome, and risk for IBD Pharmacol Ther 2015;149:191-212 IBS Pathophysiology Am J Med 2015;128:817-827 IBS & Gut Microbiota • Evidence for role of microbiota in IBS – Small intestinal bacterial overgrowth (SIBO) may initiate IBS symptoms. – Infectious gastroenteritis may trigger microinflammation (“postinfectious IBS”) Am J Med 2015;128:817-827 Brain-Gut-Enteric Microbiota Axis EMS : emotional motor system ANS : autonomic nervous system Nat Rev Gastroenterol Hepatol 2009;6:306-314 Brain-Gut-Enteric Microbiota Axis Ann Gastroenterol 2015;28:203-209. Summary : IBD vs. IBS • IBD is rare, but chronic relapsing GI inflammation • IBS is very common, functional GI disorder • IBD & IBS are multifactorial disease – Genetic factor – Environmental factor : diet – Gut microbiota – Brain-gut-microbiota axis