Adjunctive Probio-X Treatment Enhances the Therapeutic Effect of a Conventional Drug in Managing Type 2 Diabetes Mellitus by Promoting Short-Chain Fatty Acid-Producing Bacteria and Bile Acid Pathways

mSystems. 2023 Feb 23;8(1):e0130022. doi: 10.1128/msystems.01300-22. Epub 2023 Jan 23.

Abstract

Metformin is a common drug for the management of type 2 diabetes mellitus; however, it causes various adverse gastrointestinal effects, especially after prolonged treatment. It is thus of interest to identify an adjuvant treatment that synergizes with the efficacy of metformin while mitigating its adverse effects. Since previous evidence supports that the gut microbiota is a target of metformin, this study investigated the beneficial effect and mechanism of the coadministration of probiotics with metformin in the management of type 2 diabetes mellitus by conducting a 3-month randomized, double-blind, placebo-controlled clinical trial (n = 27 and 21 in the probiotic and placebo groups, respectively, who completed the trial). Clinical results showed that the coadministration of probiotics with metformin significantly reduced glycated hemoglobin compared with metformin taken alone (P < 0.05). Metagenomic and metabolomic analyses showed that the coadministration of probiotics increased the abundance of gut short-chain fatty acid (SCFA)-producing bacteria and bile acids. Significantly or marginally more bile acids and related metabolites were detected in the probiotic group than in the placebo group postintervention. Taken together, the results of our study showed that the coadministration of probiotics with metformin synergized with the hypoglycemic effect in patients with type 2 diabetes mellitus, which was likely through modulating the gut microbiome and, subsequently, SCFA and bile acid metabolism. Our findings support that cotreatment with probiotics and metformin is beneficial to patients with type 2 diabetes mellitus. IMPORTANCE Metformin causes variable adverse gastrointestinal effects, especially after prolonged treatment. We found that cotreatment with Probio-X and metformin for the management of type 2 diabetes mellitus may promote gut SCFA-producing bacteria and the levels of specific bile acids, thus increasing the secretion of related gastrointestinal hormones and ultimately improving glucose homeostasis.

Keywords: bile acids; gut microbiome; metformin; probiotics; short-chain fatty acids; type 2 diabetes mellitus.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria
  • Bile Acids and Salts / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Fatty Acids, Volatile / therapeutic use
  • Humans
  • Metformin* / therapeutic use

Substances

  • Bile Acids and Salts
  • Metformin
  • Fatty Acids, Volatile