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Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Pathogenic agents in inflammatory bowel diseases
Guillaume Pineton de Chambrun1, Jean-Frédéric Colombel, Daniel Poulain
1Clinic of Digestive Disorders and Nutrition, Hôpital Claude Huriez, CHRU Lille, France.
Purpose Of Review:
Infectious agents are still thought to be involved in the origin of inflammatory bowel disease. The focus in recent years has been more on Mycobacterium avium subsp paratuberculosis, adherent-invasive Escherichia coli or yeasts.
Recent Findings:
A metaanalysis has shown a significant association of M. avium subsp paratuberculosis and Crohn's disease and a large randomized placebo-controlled trial reported an absence of sustained beneficial effects of combined antibiotic therapy on remission of active Crohn's disease. Adherent-invasive E. coli adhere via type 1 pili to carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), abnormally expressed by intestinal epithelial cells in Crohn's disease patients. Both colonization of the ileal mucosa and stimulation of ileal epithelial cells by tumour necrosis factor-alpha induce overexpression of CEACAM6, leading to an amplification loop of colonization and inflammation. Anti-Saccharomyces cerevisiae mannan antibodies are the most prevalent serologic marker in Crohn's disease. Major oligomannose epitopes supporting antibody formation are expressed by Candida albicans in human tissues, suggesting that a loss of tolerance to C. albicans could lead to antibody formation in a subset of Crohn's disease patients who are genetically predisposed.
Summary:
M. avium subsp paratuberculosis, adherent-invasive E. coli and Candida are good candidates for an infectious aetiology of Crohn's disease on the basis of genetic susceptibility, which relates to impaired function in the defence against intracellular bacteria.
Insights
Infectious agents like Mycobacterium avium subsp paratuberculosis, Escherichia coli, and Candida may contribute to Crohn's disease. Genetic susceptibility influences the immune response to these microbes, potentially triggering inflammation.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Infectious agents are implicated in the etiology of inflammatory bowel disease.
- Recent research highlights Mycobacterium avium subsp paratuberculosis, adherent-invasive Escherichia coli, and yeasts as potential contributors.
Purpose of the Study:
- To review the evidence linking specific infectious agents to Crohn's disease.
- To explore the mechanisms of interaction between these microbes and the host immune system.
Main Methods:
- Meta-analysis of M. avium subsp paratuberculosis association with Crohn's disease.
- Review of randomized controlled trials on antibiotic therapy for Crohn's disease.
- Examination of E. coli adherence mechanisms and CEACAM6 expression.
- Analysis of serologic markers, including anti-Saccharomyces cerevisiae mannan antibodies.
- Investigation of Candida albicans' role and host immune response.
Main Results:
- A significant association between M. avium subsp paratuberculosis and Crohn's disease was found.
- Combined antibiotic therapy showed no sustained benefit for active Crohn's disease remission.
- Adherent-invasive E. coli utilizes type 1 pili to bind CEACAM6, which is overexpressed in Crohn's disease patients, creating an amplification loop.
- Anti-Saccharomyces cerevisiae mannan antibodies are prevalent in Crohn's disease.
- Loss of tolerance to Candida albicans may lead to antibody formation in genetically susceptible individuals.
Conclusions:
- Mycobacterium avium subsp paratuberculosis, adherent-invasive E. coli, and Candida are strong candidates for an infectious etiology of Crohn's disease.
- Genetic susceptibility, particularly impaired defense against intracellular bacteria, plays a crucial role in disease development.
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