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Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model

Glucagon-like peptide-1 (GLP-1) reduces postprandial hyperglycaemia, but its short half-life inhibits clinical application. The aim of the current study was to evaluate the treatment efforts of an engineered strain, Lactobacillus plantarum-pMG36e-GLP-1 (L. plantarum-pMG36e-GLP-1), that continuously...

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Autores principales: Luo, Jie, Zhang, Hongfei, Lu, Jiachen, Ma, ChaoLin, Chen, Tingtao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455315/
https://www.ncbi.nlm.nih.gov/pubmed/34584995
http://dx.doi.org/10.1016/j.synbio.2021.09.009
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author Luo, Jie
Zhang, Hongfei
Lu, Jiachen
Ma, ChaoLin
Chen, Tingtao
author_facet Luo, Jie
Zhang, Hongfei
Lu, Jiachen
Ma, ChaoLin
Chen, Tingtao
author_sort Luo, Jie
collection PubMed
description Glucagon-like peptide-1 (GLP-1) reduces postprandial hyperglycaemia, but its short half-life inhibits clinical application. The aim of the current study was to evaluate the treatment efforts of an engineered strain, Lactobacillus plantarum-pMG36e-GLP-1 (L. plantarum-pMG36e-GLP-1), that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus (T2DM) monkeys. After 7 weeks of oral supplementation with L. plantarum-pMG36e-GLP-1, the fasting blood glucose (FPG) of monkeys was significantly (p < 0.05) reduced to a normal level and only a small amount of weight was lost. The results of metagenomic sequencing showed that L. plantarum-pMG36e-GLP-1 caused a substantial (p < 0.05) reduction in the intestinal pathogen Prevotella and marked enhancement of butyrate-producing Alistipes genera. According to the functional analysis using Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, 19 metabolism-related pathways were significantly enriched in T2DM monkeys after treatment with L. plantarum-pMG36e-GLP-1. LC-MS faecal metabolomics analysis found 41 significant differential metabolites (11 higher and 30 lower) in monkeys after treatment pathways linked to the metabolism of cofactors and vitamins were the most relevant. The present study suggests that L. plantarum-pMG36e-GLP-1 had an impact on the gut microbial composition and faecal metabolomic profile in spontaneous T2DM monkeys and may be a novel candidate for diabetes treatment.
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spelling pubmed-84553152021-09-27 Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model Luo, Jie Zhang, Hongfei Lu, Jiachen Ma, ChaoLin Chen, Tingtao Synth Syst Biotechnol Article Glucagon-like peptide-1 (GLP-1) reduces postprandial hyperglycaemia, but its short half-life inhibits clinical application. The aim of the current study was to evaluate the treatment efforts of an engineered strain, Lactobacillus plantarum-pMG36e-GLP-1 (L. plantarum-pMG36e-GLP-1), that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus (T2DM) monkeys. After 7 weeks of oral supplementation with L. plantarum-pMG36e-GLP-1, the fasting blood glucose (FPG) of monkeys was significantly (p < 0.05) reduced to a normal level and only a small amount of weight was lost. The results of metagenomic sequencing showed that L. plantarum-pMG36e-GLP-1 caused a substantial (p < 0.05) reduction in the intestinal pathogen Prevotella and marked enhancement of butyrate-producing Alistipes genera. According to the functional analysis using Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, 19 metabolism-related pathways were significantly enriched in T2DM monkeys after treatment with L. plantarum-pMG36e-GLP-1. LC-MS faecal metabolomics analysis found 41 significant differential metabolites (11 higher and 30 lower) in monkeys after treatment pathways linked to the metabolism of cofactors and vitamins were the most relevant. The present study suggests that L. plantarum-pMG36e-GLP-1 had an impact on the gut microbial composition and faecal metabolomic profile in spontaneous T2DM monkeys and may be a novel candidate for diabetes treatment. KeAi Publishing 2021-09-17 /pmc/articles/PMC8455315/ /pubmed/34584995 http://dx.doi.org/10.1016/j.synbio.2021.09.009 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Luo, Jie
Zhang, Hongfei
Lu, Jiachen
Ma, ChaoLin
Chen, Tingtao
Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model
title Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model
title_full Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model
title_fullStr Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model
title_full_unstemmed Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model
title_short Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model
title_sort antidiabetic effect of an engineered bacterium lactobacillus plantarum-pmg36e -glp-1 in monkey model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455315/
https://www.ncbi.nlm.nih.gov/pubmed/34584995
http://dx.doi.org/10.1016/j.synbio.2021.09.009
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