Certain enteric pathogens are associated with higher risk of incident inflammatory bowel disease (IBD), while others could be protective, according to a study published in Alimentary Pharmacology and Therapeutics.
Disturbances in gut microbiota may result in IBD. However, the initiating events and determinants of recurrent, persistent immune dysregulation leading to chronic gastrointestinal (GI) inflammation remain unclear. In this investigation, researchers conducted a comprehensive systematic review to elucidate the role of GI infections as environmental determinants of new-onset IBD.
Researchers identified studies assessing IBD and GI infections using electronically available databases through July 2019. Inclusion criteria comprised: diagnosis of IBD; diagnosis of GI infection; ability to confirm that no individuals had IBD at the study inception; adequate information provided for comparative effect estimates; and full-text availability in English. Inclusion criteria were broader for translational studies accessing mechanisms of GI infections and predisposition to or protection from IBD.
In total, 63 studies met the full inclusion criteria. Among population-based studies of gastroenteritis, the presence of bacteria including the Salmonella species, Campylobacter species, and Clostridioides difficile demonstrated positive associations with the development of incident IBD. The researchers analyzed a national cohort study from Denmark evaluating 49,420 stool cultures positive for Campylobacter species and 41,628 for Salmonella species. In this study, both ulcerative colitis (UC) and Crohn Disease (CD) were more common following an episode of gastroenteritis with a stool culture positive for Salmonella (CD IRR [incidence rate ratio] 2.2, 95% CI 1.7-2.7; UC IRR 3.0, 95% CI 2.6-3.4) or Campylobacter (CD IRR 2.2, 95% CI 1.8- 2.7; UC IRR 2.6, 95% CI 2.3-3.0) compared with patients without gastroenteritis. Additionally, a large body of evidence has consistently shown an inverse relationship between Helicobacter pylori (H. pylori) and helminth infections and incident IBD. In a meta-analysis consisting of 40 case-control studies with 6,130 IBD cases and 74,659 controls, H. pylori exposure was associated with 57% lower odds of IBD (pooled odds ratio [pOR] 0.43, 95% CI: 0.36-0.50). This effect was more pronounced for CD (pOR 0.38, 95% CI: 0.31- 0.47) compared with UC (pOR 0.53, 95% CI: 0.44-0.65).
The limitations of the present study are that causality was not definitively established and the methodological limitations of research that are included in the review.
The authors conclude that putative mechanisms involve multiple microbial and immunologic pathways. “Prospective studies are required to clarify the clinical implications of these enteric pathogens on the risk and course of IBD, not to mention possible therapeutic or preventative benefit.”
Axelrad JE, Cadwell KH, Colombel J, Shah SC. Systematic review: gastrointestinal infection and incident inflammatory bowel disease (published online May 5, 2020). Aliment Pharmacol Ther. doi.org/10.1111/apt.15770