Microbiota and mucosal defense in IBD: an update

ABSTRACT

Introduction: Inflammatory bowel diseases (IBD) are on the rise worldwide. This review covers the current concepts of the etiology of Crohn´s disease and ulcerative colitis by focusing on an unbalanced interaction between the intestinal microbiota and the mucosal barrier. Understanding these issues is of paramount importance for the development of targeted therapies aiming at the disease cause.

Area covered: Gut microbiota alterations and a dysfunctional intestinal mucosa are associated with IBD. Here we focus on specific defense structures of the mucosal barrier, namely antimicrobial peptides and the mucus layer, which keep the gut microbiota at a distance under healthy conditions and are defective in IBD.

Expert commentary: The microbiology of both forms of IBD is different but characterized by a reduced bacterial diversity and richness. Abundance of certain bacterial species is altered, and the compositional changes are related to disease activity. In IBD the mucus layer above the epithelium is contaminated by bacteria and the immune reaction is dominated by the antibacterial response. Human genetics suggest that many of the basic deficiencies in the mucosal response, due to Paneth cell, defensin and mucus defects, are primary. Nutrition may also be important but so far there is no therapy targeting the mucosal barrier.

KEYWORDS:

• Antimicrobial peptides
• Crohn’s Disease
• defensins
• gut microbiota
• IBD
• mucosal barrier
• mucus
• probiotics
• ulcerative Colitis

Article highlights

• A dysfunctional interaction between the gut microbiota and the intestinal mucosal barrier is a hallmark of IBD.

• Changes in gut microbiota composition during IBD are inconsistent between studies.

• Are gut microbiota alterations cause (hen) or consequence (egg) of IBD?

• Antimicrobial peptides and intestinal mucus are key elements of intestinal barrier function that are defective during IBD.

• Targeting the gut microbiota to strengthen intestinal barrier function may become a successful strategy to treat IBD in the future.

Acknowledgments

The authors thank Stephanie Bügler-Mietens for administrative assistance with the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Work in the authors' laboratory is supported by Vetenskapsrådet (Swedish Research Council) through a starting grant (2018-02095) and by Åke Wibergs stiftelse (M18-0029).