Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice

Biomed Pharmacother. 2020 May;125:109914. doi: 10.1016/j.biopha.2020.109914. Epub 2020 Feb 5.

Abstract

Backgroud/aim: Previous studies have found that probiotic fermented camel milk has anti-diabetic effect by inducing (glucagon-like peptide-1) GLP-1 secretion. Probiotics are valuable in prevention and treatment of diabetes. As a result, our team islolated 14 probiotics from fermented camel milk. These probiotics have beneficial characteristics, but the possible anti-diabetic mechanisms remains unclear. The present study aimed to explore the possoble anti-diabetic mechanisms of 14 probiotics.

Methods: C57BL/Ks mice were normal group. The db/db mice were randomized into five groups: model group, metformin group, liraglutide group, low-dose and high-dose probiotic group. Biochemical parameters were determined by the respective assay kits. The levels of the short-chain fatty acids (SCFAs) and microbiota were respectively determined by gas chromatography and qRT-PCR. HE staining and immunofluorescence were used for histomorphological observation. Quantitative PCR and western-blot were determined the gene and protein expression of Bax, Bcl-2, Caspase-3 and PI3K/AKT.

Results: Probiotics significantly improved blood glucose and blood lipid parameters, as well as the morphological changes of pancreas, liver and kidney. Probiotics improved the gut barrier function through increasing the levels of SCFA-producing bacteria and SCFAs as well as the expression of claudin-1 and mucin-2, and decreasing Escherichia coli and LPS level. In additon, probiotics enhanced insulin secretion through glucose-triggered GLP-1 secretion by upregulating G protein-coupled receptor 43/41 (GPR43/41), proglucagon and proconvertase 1/3 activity. Forthermore, probiotics protected pancreas against apoptosis, which may be dependent on the upregulation of PI3K/AKT pathway.

Conclusions: The anti-diabetic effect of 14 probiotics in db/db mice seem to be related to an increase of SCFA-producing bacteria, the improvement of intestinal barrier function and the upregulation of GLP-1 production, and indicate these probiotics might be a good candidate to prevent and treat diabetes.

Keywords: Composite probiotics; Diabetes 2 mellitus; Glucagon-like peptide-1; Gut microbiota; Short-chain fatty acids.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Camelus
  • Cholesterol / blood
  • Diabetes Mellitus, Experimental / diet therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / physiology
  • Glucagon-Like Peptide 1 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / administration & dosage*

Substances

  • Blood Glucose
  • Glucagon-Like Peptide 1
  • Cholesterol