Abstract

Diabetes mellitus is a rapidly expanding global health challenge driven by complex interactions between genetic, 
environmental, metabolic, and immunological factors. Growing evidence highlights the gut microbiome as a 
critical regulator of glucose homeostasis, insulin sensitivity, immune modulation, and pancreatic β-cell function. 
This narrative review synthesizes current knowledge on the role of the human microbiome in the pathophysiology 
of both type 1 and type 2 diabetes. It examines how early-life microbial exposures influence immune tolerance and 
autoimmunity, how gut dysbiosis contributes to β-cell destruction, insulin resistance, and metabolic inflammation, 
and how microbial metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides mediate host
microbe interactions along the gut–liver–pancreas axis. The review further evaluates emerging therapeutic 
strategies, including dietary modulation, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, 
alongside methodological challenges inherent in microbiome research. While microbiome-targeted interventions 
hold considerable promise, significant gaps remain regarding causality, reproducibility, and long-term clinical 
efficacy. Addressing these challenges through well-designed longitudinal and multi-omic studies will be essential 
to translating microbiome science into effective preventive and therapeutic strategies for diabetes.