Post-infection Irritable Bowel Syndrome

Abstract

Epidemiologic data support that acute gastrointestinal infection is one of the strongest risk factors for development of irritable bowel syndrome (IBS). Risk of post-infection IBS (PI-IBS) seems to be greater with bacterial and protozoal than viral enterocolitis. Younger individuals, women, and those with severe enterocolitis are more likely to develop PI-IBS. Disease mechanisms in animal models and humans involve chronic perturbation of intestinal microbiome, epithelial and neuronal remodeling, and immune activation. These mechanisms can lead to luminal (increased proteolytic activity, altered bile acid composition) and physiologic (increased permeability, transit changes, and visceral hypersensitivity) alterations that can mediate PI-IBS symptoms.

Keywords: Bacteria; Barrier function; Diarrhea; Gut-brain axis; Infectious gastroenteritis; Inflammation; Microbiome.

Figure 1.. Diagnostic and therapeutic approach for post-infection irritable bowel syndrome.

The presence of severe symptoms, significant weight loss, abnormal physical findings or testing when diagnosing PI-IBS, as well as lack of treatment response after 4–8 weeks, warrants considering for other etiologies. Further diagnostic tests should be selected based on clinical suspicion. Pharmacologic treatment recommendations include focus on IBS-M and IBS-D which account for the vast majority of PI-IBS patients. Antispasmodics (peppermint oil, dicyclomine, hyoscine, pinaverium), TCAs (amitryptiline, imipramine, desipramine), probiotics (Bifidobacterium sp., Lactobacillus plantarum), antidiarrheals (loperamide, eluxadoline), bile acid sequestrants (cholestyramine, colesevelam, colestipol), 5HT₃ antagonists (ondansetron, alosetron, ramosetron). In the case of IBS-C, the treatment recommendations for the altered bowel habit are soluble fibers (psyllium), osmotic laxatives (polyethylene glycol, lactulose) and intestinal secretagogues (linaclotide, lubiprostone, plecanatide). Abbreviations: FODMAP, fermentable oligosaccharides, disaccharides, monosaccharides and polyols; TCAs, tricyclic antidepressants; 5HT₃, 5-hydroxytryptamine type 3; IBD, inflammatory bowel disease. Modified from Barbara G, Grover M, Bercik P, et al. Rome Foundation working team report on post-infection irritable bowel syndrome. Gastroenterology 2019;156:46–58 e7.

Figure 2.. Natural history of post-infection irritable bowel syndrome.

Within 1 year after an acute gastrointestinal infection (bacterial, viral, parasitic and overall), there is a 4-fold increase in risk for development of irritable bowel syndrome compared to non-exposed individuals. Risk decreases beyond 1 year of infection, but remains significantly increased, except in viral enteritis. *Non-significant. Abbreviations: RR, relative risk (compared to unexposed derived from same population). Not all studies had unexposed controls; hence prevalence and RR estimates not from completely overlapping studies. Data from Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: A systematic review and meta-analysis. Gastroenterology 2017;152:1042–54 e1.

Figure 3.. Alterations in the intestinal environment underlying the pathophysiology of post-infection irritable bowel syndrome.

The development of PI-IBS after acute infectious enterocolitis may be due to number of changes in intestinal microbiome, mucosal, immune or neuronal function. Microbiota changes include decreased diversity and increased Firmicutes:Bacteroides ratio. These may change luminal milieu by altering composition of bile acids, bile salts and proteases. Epithelial changes such as increased density of enteroendocrine cells, increased serotonin availability may increase intestinal motility. An altered mucosal barrier function can contribute towards immune dysregulation and neuronal hypersensitivity. Furthermore, immunophenotypic changes such as increased mast cell density, increased Th1/Th2 cell ratio and expression of proinflammatory cytokines can mediate chronic gut dysfunction as well as neuronal excitability. Lastly, inflammasome mediated depletion of neurons and nervous remodeling can affect motility and secretion. Abbreviations: 5-HT, 5-hydroxytryptamine; EC, enterochromaffin; HTRE3E, 5-hydroxytryptamine receptor 3E; IL, interleukin; PAR-2, protease activated receptor-2; SERT, serotonin transporter; TJ, tight junction; VGLUT2, vesicular glutamate transporter 2; ZO-1, zonula occludens-1; Th1/Th2, T helper type 1/2; TNF-α, tumor necrosis factor alpha.