Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Abstract

Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.

Keywords: Antimicrobial peptides; Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Gut microbiome; Biomarkers

Core Tip: Antimicrobial peptides (AMPs) play critical roles in protecting against infection while maintaining intestinal homeostasis to support commensalism with the gut microbiome. AMPs have broad spectrum antimicrobial activity with diverse mechanisms of action and regulate gut microbiome composition. Defects in endogenous AMP expression and function have been linked with animal models of inflammatory bowel disease (IBD). Exogenous delivery of AMPs such as defensins, cathelicidin, and elafin attenuates intestinal inflammation in murine models of IBD. AMPs such as calprotectin and lactoferrin are useful biomarkers for patients with IBD. Challenges with AMP stability, bioavailability, and selectivity are major barriers to their application as potential therapies.