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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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-02-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00585-19 |
| _version_ | 1818836652042223616 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:10:00Z |
| format | Article |
| id | doaj.art-a3c8e0293327400c8c26de2cadefef0a |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T03:10:00Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-a3c8e0293327400c8c26de2cadefef0a2022-12-21T20:38:03ZengAmerican Society for MicrobiologymSphere2379-50422020-02-015110.1128/mSphere.00585-19Degradation of the Incretin Hormone Glucagon-Like Peptide-1 (GLP-1) by <named-content content-type="genus-species">Enterococcus faecalis</named-content> Metalloprotease GelEStephanie L. LeValley0Catherine Tomaro-Duchesneau1Robert A. Britton2Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00585-19EnterococcusGLP-1GelEgut hormoneprotease |
| spellingShingle | 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 mSphere Enterococcus GLP-1 GelE gut hormone protease |
| 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_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_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_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 |
| topic | Enterococcus GLP-1 GelE gut hormone protease |
| url | https://journals.asm.org/doi/10.1128/mSphere.00585-19 |
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