Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE

ABSTRACT Metabolic diseases, including type 2 diabetes and obesity, have become increasingly prevalent global health concerns. Studies over the past decade have established connections between the gastrointestinal microbiota and host metabolism, but the mechanisms behind these connections are only b...

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Autores principales:	Stephanie L. LeValley, Catherine Tomaro-Duchesneau, Robert A. Britton
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Enterococcus GLP-1 GelE gut hormone protease Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a3c8e0293327400c8c26de2cadefef0a
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spelling	oai:doaj.org-article:a3c8e0293327400c8c26de2cadefef0a2021-11-15T15:27:52ZDegradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE10.1128/mSphere.00585-192379-5042https://doaj.org/article/a3c8e0293327400c8c26de2cadefef0a2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00585-19https://doaj.org/toc/2379-5042ABSTRACT Metabolic diseases, including type 2 diabetes and obesity, have become increasingly prevalent global health concerns. Studies over the past decade have established connections between the gastrointestinal microbiota and host metabolism, but the mechanisms behind these connections are only beginning to be understood. We were interested in identifying microbes that have the ability to modulate the levels of the incretin hormone glucagon-like peptide-1 (GLP-1). Using a human-derived cell line that is capable of secreting GLP-1 in response to stimulatory ligands (NCI-H716), we identified supernatants from several bacterial isolates that were capable of decreasing GLP-1 levels, including several strains of Enterococcus faecalis. We further identified the secreted protease GelE, an established virulence factor from E. faecalis, as being responsible for GLP-1 inhibition via direct cleavage of GLP-1 by GelE. Finally, we demonstrated that E. faecalis supernatants can disrupt a colonic epithelial monolayer and cleave GLP-1 in a gelE-dependent manner. This work suggests that a secreted factor from an intestinal microbe can traverse the epithelial barrier and impact levels of an important intestinal hormone. IMPORTANCE Humans have a complex and interconnected relationship with their gastrointestinal microbiomes, yet our interest in the microbiome tends to focus on overt pathogenic or probiotic activities, leaving the roles that commensal species may have on host physiology and metabolic processes largely unexplored. Commensal organisms in the microbiome produce and secrete many factors that have an opportunity to interact with the gastrointestinal tract and host biology. Here, we show that a secreted protease from E. faecalis, GelE, is able to degrade the gastrointestinal hormone GLP-1, which is responsible for regulating glucose homeostasis and appetite in the body. The disruption of natural GLP-1 signaling by GelE may have significant consequences for maintaining healthy blood glucose levels and in the development of metabolic disease. Furthermore, this work deepens our understanding of specific host-microbiome interactions.Stephanie L. LeValleyCatherine Tomaro-DuchesneauRobert A. BrittonAmerican Society for MicrobiologyarticleEnterococcusGLP-1GelEgut hormoneproteaseMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterococcus GLP-1 GelE gut hormone protease Microbiology QR1-502
spellingShingle	Enterococcus GLP-1 GelE gut hormone protease Microbiology QR1-502 Stephanie L. LeValley Catherine Tomaro-Duchesneau Robert A. Britton Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE
description	ABSTRACT Metabolic diseases, including type 2 diabetes and obesity, have become increasingly prevalent global health concerns. Studies over the past decade have established connections between the gastrointestinal microbiota and host metabolism, but the mechanisms behind these connections are only beginning to be understood. We were interested in identifying microbes that have the ability to modulate the levels of the incretin hormone glucagon-like peptide-1 (GLP-1). Using a human-derived cell line that is capable of secreting GLP-1 in response to stimulatory ligands (NCI-H716), we identified supernatants from several bacterial isolates that were capable of decreasing GLP-1 levels, including several strains of Enterococcus faecalis. We further identified the secreted protease GelE, an established virulence factor from E. faecalis, as being responsible for GLP-1 inhibition via direct cleavage of GLP-1 by GelE. Finally, we demonstrated that E. faecalis supernatants can disrupt a colonic epithelial monolayer and cleave GLP-1 in a gelE-dependent manner. This work suggests that a secreted factor from an intestinal microbe can traverse the epithelial barrier and impact levels of an important intestinal hormone. IMPORTANCE Humans have a complex and interconnected relationship with their gastrointestinal microbiomes, yet our interest in the microbiome tends to focus on overt pathogenic or probiotic activities, leaving the roles that commensal species may have on host physiology and metabolic processes largely unexplored. Commensal organisms in the microbiome produce and secrete many factors that have an opportunity to interact with the gastrointestinal tract and host biology. Here, we show that a secreted protease from E. faecalis, GelE, is able to degrade the gastrointestinal hormone GLP-1, which is responsible for regulating glucose homeostasis and appetite in the body. The disruption of natural GLP-1 signaling by GelE may have significant consequences for maintaining healthy blood glucose levels and in the development of metabolic disease. Furthermore, this work deepens our understanding of specific host-microbiome interactions.
format	article
author	Stephanie L. LeValley Catherine Tomaro-Duchesneau Robert A. Britton
author_facet	Stephanie L. LeValley Catherine Tomaro-Duchesneau Robert A. Britton
author_sort	Stephanie L. LeValley
title	Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE
title_short	Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE
title_full	Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE
title_fullStr	Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE
title_full_unstemmed	Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE
title_sort	degradation of the incretin hormone glucagon-like peptide-1 (glp-1) by <named-content content-type="genus-species">enterococcus faecalis</named-content> metalloprotease gele
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/a3c8e0293327400c8c26de2cadefef0a
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Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelE

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