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

  • 2021-12
  • Synthetic and Systems Biotechnology 6(4)
    • Jie Luo
    • Hongfei Zhang
    • Jiachen Lu
    • Chaolin Ma
    • Tingtao Chen

Abstract

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.

Keywords: Faecal metabolomics; Gut microbiome; L. plantarum-pMG36e-GLP-1; T2DM.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactobacillus plantarum UALp-05Altered Fecal Metabolite ProfileNeutral
Moderate
Lactobacillus plantarum UALp-05Enhanced Metabolic Pathway ActivationBeneficial
Moderate
Lactobacillus plantarum UALp-05Increased Butyrate-producing AlistipesBeneficial
Large
Lactobacillus plantarum UALp-05Reduced Body WeightNeutral
Small
Lactobacillus plantarum UALp-05Reduced Fasting Blood Sugar LevelsBeneficial
Large
Lactobacillus plantarum UALp-05Reduced Intestinal Pathogen PrevotellaBeneficial
Large
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