<p>Type 2 Diabetes Mellitus (T2DM) is increasingly recognized as increasingly recognized as not only a metabolic disorder, but also a disease of microbiome–host dysregulation. While the role of the gut microbiota in T2DM has been extensively studied, the emerging convergence of precision medicine and microbiome modulation has not been systematically integrated into prior reviews. This work provides a critical synthesis that unites the classical concepts of dysbiosis with cutting-edge insights into microbial metabolites, strain-specific effects, and host–microbe–drug interactions, including the influence of metformin on microbial ecology and the therapeutic potential of <i>Akkermansia muciniphila</i>. We further discuss the underexplored domains, such as the gut virome, microbial gene editing, and short-chain fatty acid subtype-targeted interventions, which may transform T2DM management. We propose a novel conceptual framework for microbiome-guided, individualized T2DM care by framing gut microbiota as a dynamic, patient-specific therapeutic target. The review concludes with a roadmap for translating microbiota signatures into predictive biomarkers and tailored interventions, emphasizing standardized methodologies, multi-omics integration, and cross-disciplinary clinical trials. This perspective shifts the field from descriptive correlations to actionable precision-guided microbiome therapeutics in T2DM. Notably, this review extends beyond existing summaries by integrating emerging concepts, including gut virome contributions, microbial metabolite engineering, and host–microbe–drug interaction frameworks, to position the gut microbiota as a precision-modifiable therapeutic axis. This synthesis not only reviews established associations but also identifies underexplored therapeutic frontiers, including the gut virome, mycobiome, and microbial genome editing, which could reshape precision T2DM management.</p>

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Modulating gut microbiota in type 2 diabetes mellitus: advances and challenges in precision medicine

  • Rasmi Madhusoodhanan,
  • Krishnamoorthi Raman,
  • Rijia Akbar,
  • Mahalingam Pambayan Ulagan,
  • Vijaya Anand Mariadoss Arokia,
  • Thiyagarajan P

摘要

Type 2 Diabetes Mellitus (T2DM) is increasingly recognized as increasingly recognized as not only a metabolic disorder, but also a disease of microbiome–host dysregulation. While the role of the gut microbiota in T2DM has been extensively studied, the emerging convergence of precision medicine and microbiome modulation has not been systematically integrated into prior reviews. This work provides a critical synthesis that unites the classical concepts of dysbiosis with cutting-edge insights into microbial metabolites, strain-specific effects, and host–microbe–drug interactions, including the influence of metformin on microbial ecology and the therapeutic potential of Akkermansia muciniphila. We further discuss the underexplored domains, such as the gut virome, microbial gene editing, and short-chain fatty acid subtype-targeted interventions, which may transform T2DM management. We propose a novel conceptual framework for microbiome-guided, individualized T2DM care by framing gut microbiota as a dynamic, patient-specific therapeutic target. The review concludes with a roadmap for translating microbiota signatures into predictive biomarkers and tailored interventions, emphasizing standardized methodologies, multi-omics integration, and cross-disciplinary clinical trials. This perspective shifts the field from descriptive correlations to actionable precision-guided microbiome therapeutics in T2DM. Notably, this review extends beyond existing summaries by integrating emerging concepts, including gut virome contributions, microbial metabolite engineering, and host–microbe–drug interaction frameworks, to position the gut microbiota as a precision-modifiable therapeutic axis. This synthesis not only reviews established associations but also identifies underexplored therapeutic frontiers, including the gut virome, mycobiome, and microbial genome editing, which could reshape precision T2DM management.