Gut microbiome–epigenetic crosstalk in obesity and type 2 diabetes: mechanisms, evidence, and translational opportunities

Obesity and type 2 diabetes mellitus are closely linked metabolic disorders in which gut microbial alterations interact with host epigenetic regulation to influence inflammation, insulin sensitivity, and energy homeostasis. This review examines the gut microbiome-epigenetics interface in these conditions by integrating mechanistic evidence with a Scopus-based bibliometric analysis of publications from 2016 to 2025, thereby providing both disease-focused synthesis and field-level context. Bibliometric mapping identified 1,153 documents from 515 sources authored by 5,445 researchers, with a marked annual growth rate of 27.79%, indicating rapid expansion of this interdisciplinary area. Mechanistically, current evidence converges on three major epigenetic domains: DNA methylation, histone modifications, and non-coding RNA regulation. Microbiota-derived metabolites, particularly short-chain fatty acids, folate-related methyl donors, and other bioactive compounds, influence enzymes such as DNA methyltransferases and histone deacetylases, as well as downstream chromatin marks and microRNA networks relevant to metabolic dysfunction. In obesity and type 2 diabetes, recurrent findings include reduced abundance of butyrate-producing taxa and enrichment of pro-inflammatory or endotoxin-associated bacteria, although these patterns remain heterogeneous across populations, study designs, and analytical methods. Accordingly, the review emphasizes that phylum-level or taxa-level associations should be interpreted cautiously and that causality remains incompletely resolved. A key contribution of this review is the combined evaluation of mechanistic pathways, context-dependent microbial signatures, and translational limitations within a single framework. Overall, microbiome-targeted interventions remain promising but insufficiently validated, and progress toward clinical application will require longitudinal, multi-omics, and interventional studies that directly link specific taxa, metabolites, and epigenetic modifications.