Antimicrobial Peptides and the Gut Microbiome in Inflammatory Bowel Disease

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2021 Dec 10

PMID 34887639

Citations 41

Authors

John Gubatan

Derek R Holman

Christopher J Puntasecca

Danielle Polevoi

Samuel Js Rubin

Stephan Rogalla

Affiliations

Soon will be listed here.

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.

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References

Pous-Serrano S, Frasson M, Cerrillo E, Beltran B, Iborra M, Hervas D . Correlation between fecal calprotectin and inflammation in the surgical specimen of Crohn's disease. J Surg Res. 2017; 213:290-297. DOI: 10.1016/j.jss.2017.02.064. View

Marin M, Holani R, Blyth G, Drouin D, Odeon A, Cobo E . Human cathelicidin improves colonic epithelial defenses against Salmonella typhimurium by modulating bacterial invasion, TLR4 and pro-inflammatory cytokines. Cell Tissue Res. 2019; 376(3):433-442. DOI: 10.1007/s00441-018-02984-7. View

Hashimoto S, Uto H, Kanmura S, Sakiyama T, Oku M, Iwashita Y . Human neutrophil peptide-1 aggravates dextran sulfate sodium-induced colitis. Inflamm Bowel Dis. 2011; 18(4):667-75. DOI: 10.1002/ibd.21855. View

Motta J, Rolland C, Edir A, Florence A, Sagnat D, Bonnart C . Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation. Mucosal Immunol. 2021; 14(3):667-678. PMC: 8075934. DOI: 10.1038/s41385-021-00375-w. View

Gennaro R, Zanetti M . Structural features and biological activities of the cathelicidin-derived antimicrobial peptides. Biopolymers. 2000; 55(1):31-49. DOI: 10.1002/1097-0282(2000)55:1<31::AID-BIP40>3.0.CO;2-9. View

Doumas S, Kolokotronis A, Stefanopoulos P . Anti-inflammatory and antimicrobial roles of secretory leukocyte protease inhibitor. Infect Immun. 2005; 73(3):1271-4. PMC: 1064911. DOI: 10.1128/IAI.73.3.1271-1274.2005. View

Hanson M, Lemaitre B, Unckless R . Dynamic Evolution of Antimicrobial Peptides Underscores Trade-Offs Between Immunity and Ecological Fitness. Front Immunol. 2019; 10:2620. PMC: 6857651. DOI: 10.3389/fimmu.2019.02620. View

Martinez-Guryn K, Hubert N, Frazier K, Urlass S, Musch M, Ojeda P . Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids. Cell Host Microbe. 2018; 23(4):458-469.e5. PMC: 5912695. DOI: 10.1016/j.chom.2018.03.011. View

Divyashree M, Mani M, Reddy D, Kumavath R, Ghosh P, Azevedo V . Clinical Applications of Antimicrobial Peptides (AMPs): Where do we Stand Now?. Protein Pept Lett. 2019; 27(2):120-134. DOI: 10.2174/0929866526666190925152957. View

10.

Tai E, Wong H, Lam E, Wu W, Yu L, Koo M . Cathelicidin stimulates colonic mucus synthesis by up-regulating MUC1 and MUC2 expression through a mitogen-activated protein kinase pathway. J Cell Biochem. 2007; 104(1):251-8. DOI: 10.1002/jcb.21615. View

11.

Schoepfer A, Beglinger C, Straumann A, Trummler M, Vavricka S, Bruegger L . Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol. 2009; 105(1):162-9. DOI: 10.1038/ajg.2009.545. View

12.

Aksan A, Wohlrath M, Iqbal T, Farrag K, Dignass A, Stein J . Serum Hepcidin Levels Predict Intestinal Iron Absorption in Patients with Inflammatory Bowel Disease. Clin Lab. 2019; 65(3). DOI: 10.7754/Clin.Lab.2019.190106. View

13.

Nuding S, Frasch T, Schaller M, Stange E, Zabel L . Synergistic effects of antimicrobial peptides and antibiotics against Clostridium difficile. Antimicrob Agents Chemother. 2014; 58(10):5719-25. PMC: 4187972. DOI: 10.1128/AAC.02542-14. View

14.

Wan M, Sabirsh A, Wetterholm A, Agerberth B, Haeggstrom J . Leukotriene B4 triggers release of the cathelicidin LL-37 from human neutrophils: novel lipid-peptide interactions in innate immune responses. FASEB J. 2007; 21(11):2897-905. DOI: 10.1096/fj.06-7974com. View

15.

Salzman N . Paneth cell defensins and the regulation of the microbiome: détente at mucosal surfaces. Gut Microbes. 2011; 1(6):401-6. PMC: 3056107. DOI: 10.4161/gmic.1.6.14076. View

16.

White J . Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. J Steroid Biochem Mol Biol. 2010; 121(1-2):234-8. DOI: 10.1016/j.jsbmb.2010.03.034. View

17.

Nugteren S, Samsom J . Secretory Leukocyte Protease Inhibitor (SLPI) in mucosal tissues: Protects against inflammation, but promotes cancer. Cytokine Growth Factor Rev. 2021; 59:22-35. DOI: 10.1016/j.cytogfr.2021.01.005. View

18.

Otte J, Zdebik A, Brand S, Chromik A, Strauss S, Schmitz F . Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity. Regul Pept. 2009; 156(1-3):104-17. DOI: 10.1016/j.regpep.2009.03.009. View

19.

Chu H, Pazgier M, Jung G, Nuccio S, Castillo P, de Jong M . Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science. 2012; 337(6093):477-81. PMC: 4332406. DOI: 10.1126/science.1218831. View

20.

Tran D, Wang J, Ha C, Ho W, Mattai S, Oikonomopoulos A . Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease. BMC Gastroenterol. 2017; 17(1):63. PMC: 5427565. DOI: 10.1186/s12876-017-0619-4. View