Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome

doi:10.1053/j.gastro.2018.07.011

Gastroenterology

Volume 156, Issue 1, January 2019, Pages 46-58.e7

https://doi.org/10.1053/j.gastro.2018.07.011 Get rights and content

Background & Aims

The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience.

Methods

The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members.

Results

PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms.

Conclusions

Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.

Section snippets

Diagnosis

Although there is no validated definition of PI-IBS, this condition is characterized by new-onset, Rome criteria–positive IBS after an episode of acute gastroenteritis in individuals who did not have IBS before the infection. The diagnostic criteria for PI-IBS proposed by the Rome Foundation Working Team (RFWT) are based on the Rome IV criteria. These criteria were not part of the original Rome IV document, because they were prepared after the release of the Rome IV publications (Table 1).

Pathophysiology

PI-IBS is a complex and likely multifactorial disorder. Studies on the pathophysiology have been performed in small groups of patients and at different time points postinfection, which may contribute to incomplete information. The pathophysiology of PI-IBS is dominated by the interaction between the central and peripheral factors, the latter including the microbiota, epithelial, enteroendocrine, immunologic, and neuromotor mechanisms. It is currently unknown if there are unique

Animal Models

Several mouse models of PI-IBS using parasitic and bacterial infections mimic certain aspects of the gut dysfunction and low-grade immune activation observed in patients. None of these models entirely recapitulates the full spectrum of IBS symptoms, and each of them provides certain advantages over the others. Figure 5 summarizes animal models for PI-IBS.

T spiralis Model

T spiralis is a nematode parasite that transiently infects the gastrointestinal tract of rats and mice and induces chronic inflammation and gut dysfunction that is maintained after the parasite expulsion.⁶⁹ The effects on the host are genetically influenced, because some mouse strains, such as outbred NIH Swiss mice, display more pronounced changes in gut function than other strains.⁷⁰ T spiralis induces long-term neuromuscular dysfunction, characterized by muscle hypercontractility and altered

Treatment and Consensus Statements

The RFWT performed a systematic literature search and found limited data and no existing guidelines or recommendations on specific management strategies for PI-IBS. Therefore, the RFWT adopted a Delphi process to rate quality of evidence on patient education regarding the condition and guidance on therapy, including the few specific treatments tested in controlled clinical trials in PI-IBS patients. Details on the Delphi process and statements assessed are provided in the supplementary

Summary

We present the following summary points:

•
PI-IBS is a common condition best characterized by Rome IV symptoms occurring in approximately 1 in 10 individuals immediately after and following resolution of acute infective gastroenteritis.
•
To date, infectious gastroenteritis is one of the strongest risk factors for the development of IBS. The fact that incident cases of IBS can be identified after an objective event such as infection has allowed us to move away from unfair cliché that IBS is a

Future Considerations

Although PI-IBS has received increasing attention, these studies are challenging. The condition is best studied prospectively, and only large outbreaks make it possible to recruit substantive numbers of patients. Future mechanistic studies should focus on pathogen-specific subgroups that could lead to identification of specific pathophysiological mechanisms. Development of biomarkers that can be used in acute stages for prevention of PI-IBS development and chronically for diagnosis and specific

Acknowledgements

We acknowledge Jerry Schoendorf for assistance with the illustrations and Lori Anderson for administrative assistance.

Author contributions: The working team was led by Giovanni Barbara and Grover Madhusudan. All working team members contributed equally to the manuscript and approved it in its final version.

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The aim of this study was to determine the risk of irritable bowel syndrome (IBS) diagnosis in patients with celiac disease (CD) compared with general population comparators.
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: Conflicts of interest Giovanni Barbara has been a consultant, served on the advisory board, or received speaker’s bureau fees and/or research support from Danone, Yakult, Ironwood, Malesci, Nestlé, Noos, Synergy, Alfa Wassermann, Almirall, and Shire; Grover Madhusudan has served on the advisory board or received research support from Takeda, Dong-A, Ironwood, and Napo; Premysl Bercik has been a consultant, served on the advisory board, and/or received research support from Nestlé, Allergan, Lupin Pharmaceuticals, IM HealthScience, and Innovate Biopharmaceuticals; Maura Corsetti acts as a consultant for Allergan and Kyowa Kirin and has been speaker for Shire and Menarini; Lena Ohman has served on the advisory board of Genetic Analyses and received research support from Danone and AstraZeneca. The remaining authors disclose no conflicts.

: Funding This work is supported by Rome Foundation, North Carolina. In addition, the authors would like to acknowledge the following funding sources: Italian Ministry of Education, University and Research; Fondazione del Monte di Bologna e Ravenna and IMA (to Giovanni Barbara) and National Institute of Diabetes and Digestive and Kidney Diseases K23 103911 (to Grover Madhusudan).

View full text

Original ResearchFull Report: Clinical—Alimentary TractRome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome

Background & Aims

Methods

Results

Conclusions

Section snippets

Diagnosis

Pathophysiology

Animal Models

T spiralis Model

Treatment and Consensus Statements

Summary

Future Considerations

Acknowledgements

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Am J Gastroenterol

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Am J Pathol

Eur J Pharmacol

Gastroenterology

Post-dysenteric colitis

Br Med J

The irritable colon syndrome. A study of the clinical features, predisposing causes, and prognosis in 130 cases

Q J Med

The role of psychological and biological factors in postinfective gut dysfunction

Gut

Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients

Br Med J

Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis

Gastroenterology

Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study

Gut

Estimating the contribution of acute gastroenteritis to the overall prevalence of irritable bowel syndrome

J Neurogastroenterol Motil

Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario

Aliment Pharmacol Ther

Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes

Am J Gastroenterol

Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome

Gut

Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia

Aliment Pharmacol Ther

Afferent hypersensitivity in a mouse model of post-inflammatory gut dysfunction: role of altered serotonin metabolism

J Physiol

Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction

Neurogastroenterol Motil

Role of cytolethal distending toxin in altered stool form and bowel phenotypes in a rat model of post-infectious irritable bowel syndrome

J Neurogastroenterol Motil

A new rat model links two contemporary theories in irritable bowel syndrome

Dig Dis Sci

ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS

World J Gastroenterol

Interstitial cells of Cajal in health and disease

Neurogastroenterol Motil

Systematic review of animal models of post-infectious/post-inflammatory irritable bowel syndrome

J Gastroenterol

Brain-gut interactions increase peripheral nociceptive signaling in mice with postinfectious irritable bowel syndrome

Gastroenterology

Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis

Gut

Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome

Aliment Pharmacol Ther

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome—a pilot study

Scand J Gastroenterol

Bowel disorders

Gastroenterology

Clustering and stability of functional lower gastrointestinal symptom after enteric infection

Original Research
Full Report: Clinical—Alimentary Tract
Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome