Gubatan J, Holman DR, Puntasecca CJ, Polevoi D, Rubin SJ, Rogalla S. Antimicrobial peptides and the gut microbiome in inflammatory bowel disease. World J Gastroenterol 2021; 27(43): 7402-7422 [PMID: 34887639 DOI: 10.3748/wjg.v27.i43.7402]
Corresponding Author of This Article
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. jgubatan@stanford.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Frontier
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
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 byChan 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: https://creativecommons.org/Licenses/by-nc/4.0/
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. jgubatan@stanford.edu
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
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.
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.
