• The Gut Microbiome and Type 2 Diabetes: Mechanisms and Therapeutic Implications
  • Maryam Jalilian,1 Maedeh Paknia,2 Sara Mohammadi,3 Yasna Azizpour,4,*
    1. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.
    2. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.
    3. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.
    4. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.


  • Introduction: The gut microbiome, which is composed of trillions of microorganisms, is increasingly recognized as a central regulator of human health. It contributes to energy metabolism, nutrient absorption, and immune homeostasis through the production of bioactive metabolites such as short-chain fatty acids (SCFAs), bile acids, lipopolysaccharides (LPS), trimethylamine N-oxide (TMAO), and tryptophan derivatives. Beyond these metabolic functions, the microbiota maintains the integrity of the intestinal barrier and prevents the translocation of harmful microbial products into systemic circulation. Type 2 diabetes (T2D), a multifactorial metabolic disorder characterized by insulin resistance, hyperglycemia, and chronic low-grade inflammation, has been strongly associated with alterations in gut microbial composition. Dysbiosis in T2D is marked by reduced levels of beneficial bacteria such as Bifidobacterium, Faecalibacterium prausnitzii, and Akkermansia muciniphila, alongside an increase in proteolytic bacteria that produce pro-inflammatory metabolites. These changes contribute to systemic inflammation, oxidative stress, and pancreatic β-cell dysfunction, thereby exacerbating metabolic imbalance. This review aims to summarize current evidence regarding gut microbiota composition and function in T2D, the role of microbial metabolites such as short-chain fatty acids (SCFAs) in metabolic regulation, and potential microbiome-targeted interventions.
  • Methods: A narrative review was conducted by searching PubMed, Google Scholar, ResearchGate, and the NIH database. Studies published in the last 10 years focusing on gut microbiota, microbial metabolites, and interventions in type 2 diabetes were included.
  • Results: The reviewed studies consistently reveal alterations in the gut microbiota in type 2 diabetes (T2D). In both human and animal studies, beneficial bacteria such as Bifidobacterium, Faecalibacterium prausnitzii, and Akkermansia muciniphila are consistently reduced, while proteolytic and pro-inflammatory bacteria are increased. This microbial imbalance is associated with decreased production of short-chain fatty acids (SCFAs), impaired intestinal barrier function, and increased systemic exposure to bacterial metabolites such as lipopolysaccharides (LPS) and trimethylamine N-oxide (TMAO). These microbial changes contribute to insulin resistance, chronic inflammation, oxidative stress, and pancreatic β-cell dysfunction. Interventions such as high-fiber diets, probiotics, prebiotics, and metformin can partially restore microbial balance, enhance SCFA production, and reduce systemic inflammation. Overall, the evidence highlights the critical role of the gut microbiome in T2D and suggests that targeted modulation of microbial communities may improve glucose control and overall metabolic health.
  • Conclusion: The gut microbiome is a key factor in T2D pathophysiology and represents a promising target for therapy. Despite encouraging findings, challenges remain due to individual variability, methodological limitations, and lack of large-scale clinical trials. Future research should focus on identifying critical microbial species and applying integrated approaches to develop safe and personalized microbiome-based strategies for T2D prevention and management.
  • Keywords: Type 2 diabetes; gut microbiome; dysbiosis; probiotics; prebiotics;