Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms

Shunsuke Kato,Takehiro Sato,Yuichiro Yamada,Yuichiro Yamada,Hiroki Fujita,Masahiro Kawatani,Masahiro Kawatani

doi:10.1038/s41598-021-88612-x

Shunsuke Kato, Takehiro Sato + Show 5 more

Open Access

https://doi.org/10.1038/s41598-021-88612-x

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Journal: Scientific Reports	Publication Date: Apr 28, 2021
Citations: 17	License type: open-access

Affiliation: Akita University, Nagoya University

Abstract

There is a close relationship between the gut microbiota and metabolic disorders. In this study, acute administration of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide to mice increased the cecal levels of caseinolytic protease B, a component of Escherichia coli, and of norepinephrine. Chemical sympathectomy blocked these events. Norepinephrine was found to pass into the intestinal lumen in vitro. c-Fos staining of the intermediolateral nucleus was identified as indirect evidence of sympathetic nervous system activation of the intestinal tract by GLP-1RA. Under normal conditions, the increase in E. coli did not affect the host. However, in mice with colitis, bacterial translocation was observed with attenuation of tight junction gene expression. This is the first study to investigate the unique underlying mechanisms related the effects of GLP-1RA on changes in the gut bacterium.

Highlights

There is a close relationship between the gut microbiota and metabolic disorders
NE is present in the intestinal lumen[24], it is not clear whether NE in the intestinal tissue is released into the intestinal lumen and there appear to be no reports of NE-mediated increases in E. coli in vivo
We showed that acute administration of liraglutide increased the expression of Caseinolytic protease B (ClpB) by about 400-fold compared with the control (Fig. 1B)

Summary

Introduction

Acute administration of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide to mice increased the cecal levels of caseinolytic protease B, a component of Escherichia coli, and of norepinephrine. In mice with colitis, bacterial translocation was observed with attenuation of tight junction gene expression This is the first study to investigate the unique underlying mechanisms related the effects of GLP-1RA on changes in the gut bacterium. Certain types of E. coli have been reported to activate host intestinal defense factors and inhibit the growth of other harmful gut bacteria, and their roles are expected to be diverse[12,13]. NE is present in the intestinal lumen[24], it is not clear whether NE in the intestinal tissue is released into the intestinal lumen and there appear to be no reports of NE-mediated increases in E. coli in vivo

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Results

Conclusion