Pharmacomicrobiomics: Exploring the role of gut microbiota in type 2 diabetes and antidiabetic drug mechanisms.

BACKGROUND AND AIM: The gut microbiota is intricately linked to the pathogenesis of type 2 diabetes mellitus (T2DM). This review aims to explore the bidirectional interaction between antidiabetic drugs and the gut microbiota, focusing on how drugs modulate the microbiome to exert therapeutic effects and how this interaction influences common drug side effects, thereby outlining the role of pharmacomicrobiomics in personalizing T2DM treatment.

METHODS AND

RESULTS

We comprehensively reviewed literature from PubMed, Scopus, and Embase on gut microbiota, T2DM, and antidiabetic drugs. Evidence indicates that various drug classes (e.g., metformin, sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists (RAs), α-glucosidase inhibitors (AGIs)) significantly alter gut microbial composition (e.g., Bacteroidetes - to -Firmicutes ratio), functionality, and metabolite production (e.g., SCFAs, bile acids). These changes contribute not only to glycemic control but also to the drugs' cardiorenal benefits. Conversely, the microbiota influences drug metabolism and is implicated in the manifestation of typical side effects, such as gastrointestinal disturbances from metformin and acarbose.

CONCLUSIONS

The gut microbiota is a crucial mediator of both the efficacy and toxicity of antidiabetic drugs. Understanding pharmacomicrobiomics provides a novel framework for developing personalized therapeutic strategies in T2DM, potentially using an individual's microbiome as a biomarker for drug selection and side effect prediction.