Gut microbiota as a key player in diabetes mellitus: mechanisms, dysbiosis, and emerging interventions
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Saiyad Bastaminejad1, Salar Bakhtiyari2,3, Amin Heidari4
1Department of Genetics and Molecular Medicine, School of ParaMedicine, Ilam University of Medical Sciences, Ilam, Iran.
Abstract:
The gut microbiome has emerged as a critical regulator of metabolic and immune homeostasis, with significant implications for diabetes mellitus. This narrative review synthesizes findings from selected landmark original investigations published from 2000 to 2026, examining the role of the gut microbiome in both type 1 diabetes (T1D) and type 2 diabetes (T2D). As a narrative rather than a systematic review, this synthesis does not follow a registered protocol or an exhaustive, reproducible search strategy. Observational studies frequently report dysbiosis, characterized by reduced microbial diversity and altered taxa, as a feature of both prediabetes and diabetes, correlating with poor glycemic control and complications, although the specific taxa and dysbiotic signatures implicated vary across geographically and ethnically distinct populations, indicating that dysbiosis is not a uniform, population-invariant hallmark of disease. Mechanistic studies highlight pathways such as short-chain fatty acid production, immune modulation, and gut barrier integrity, which mediate microbial effects on insulin sensitivity and glucose metabolism, with short-chain fatty acid (SCFA) signaling and gut barrier integrity identified as the most significant pathways driving these effects. Interventional approaches, including probiotics, prebiotics, dietary modifications, fasting, exercise, and bariatric surgery, show preliminary, proof-of-concept potential to reshape the microbiome and improve diabetic outcomes, although none of these interventions has yet been validated in large-scale, adequately powered, multi-center randomized controlled trials with hard clinical endpoints, and none should be regarded as an established treatment. Notably, T1D research emphasizes autoimmune interactions, while T2D focuses on metabolic dysfunction. Despite advances, challenges like establishing causality and addressing inter-individual variability persist. This review underscores the microbiome's therapeutic promise pending confirmation in the larger trials outlined above, and advocates for personalized, multi-omics-driven strategies to enhance diabetes management.
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