Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2021; 27(43): 7402-7422
Published online Nov 21, 2021. doi: 10.3748/wjg.v27.i43.7402
Antimicrobial peptides and the gut microbiome in inflammatory bowel disease
John Gubatan, Derek R Holman, Christopher J Puntasecca, Danielle Polevoi, Samuel JS Rubin, Stephan Rogalla
John Gubatan, Stephan Rogalla, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
Derek R Holman, Department of Radiology, Molecular Imaging Program at Stanford , Stanford University, Stanford , CA 94305, United States
Christopher J Puntasecca, Danielle Polevoi, Samuel JS Rubin, Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
Author contributions: Gubatan J organized and led the literature review; Gubatan J, Holman DR, Puntasecca CJ, Polevoi D, Rubin SJS, and Rogalla S performed the primary literature and data extraction. Gubatan J reviewed literature search results; Gubatan J, Holman DR, Puntasecca CJ, and Polevoi D drafted the manuscript; Rogalla S provided critical review of the manuscript; All authors interpreted the results and contributed to critical review of the manuscript; Gubatan J had full access to the study data and takes responsibility for the integrity of the data and accuracy of the analysis.
Supported by Chan Zuckerberg Biohub Physician Scientist Scholar Award; and National Institutes of Health NIDDK Clinical Research Loan Repayment Program Award.
Conflict-of-interest statement: The authors have no conflicts of interests or financial disclosures relevant to this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: John Gubatan, MD, Consultant Physician-Scientist, Postdoctoral Fellow, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 420 Broadway Street Pavilion D, 2nd Floor , Redwood City, CA 94063, United States.
Received: March 19, 2021
Peer-review started: March 19, 2021
First decision: May 1, 2021
Revised: May 13, 2021
Accepted: November 15, 2021
Article in press: November 15, 2021
Published online: November 21, 2021

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.