Asian Journal of Medical Principles and Clinical Practice

Type 2 diabetes mellitus remains one of the principal drivers of global non-communicable disease burden, and impaired secretion or action of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide is now recognised as a core feature of its pathophysiology. Over the past two decades, the gut microbiota has emerged as an unexpected but influential regulator of this axis. Bacterial fermentation products such as short-chain fatty acids, microbially transformed bile acids, lipopolysaccharide, and amino acid derivatives interact with enteroendocrine L- and K-cells through dedicated receptors and signalling pathways, thereby shaping postprandial hormone output and downstream glycaemic control. This review synthesises mechanistic, observational, and interventional evidence describing how compositional and functional alterations of the intestinal microbiota influence incretin physiology and contribute to insulin resistance and hyperglycaemia. It traces the route from bacterial metabolite production, through G-protein-coupled receptor and nuclear receptor signalling, to enteroendocrine hormone release, and considers how individual taxa, dietary fibre, probiotics, faecal microbiota transplantation, bariatric surgery, and existing glucose-lowering drugs each intersect with this pathway. Particular attention is given to the bidirectional relationship between glucose-lowering agents and the microbiome, including emerging evidence that bacterial dipeptidyl peptidase-4 homologues may blunt incretin efficacy. The review closes by outlining priority research directions, drawing overall conclusions, and identifying the principal limitations of the current evidence base, with the aim of clarifying where microbiome-informed approaches might realistically refine the prevention and management of type 2 diabetes mellitus.