{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:22Z","timestamp":1787029222382,"version":"build-2736575974"},"reference-count":114,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Persistent racial and ethnic disparities in type 2 diabetes mellitus (T2DM) are incompletely explained by genetic susceptibility, obesity, lifestyle, and socioeconomic factors, suggesting that additional biological mechanisms may link environmental exposures to metabolic disease risk. Increasing evidence indicates that the exposome, encompassing environmental exposures across the life course, may influence long-term metabolic health through molecular mechanisms that integrate environmental signals with host biology. This Review synthesizes epidemiological, experimental, and mechanistic evidence on the gut microbiota\u2013host epigenetic axis and its potential role in linking environmental exposures to population differences in T2DM susceptibility. Gut microbial dysbiosis alters the production and metabolism of short-chain fatty acids, bile acids, and tryptophan-derived metabolites. These microbial metabolites can modulate host signaling and epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA activity, which may influence the expression of genes involved in glucose homeostasis, inflammation, and insulin sensitivity. Conversely, host epigenetic programs may influence intestinal barrier integrity and immune responses, thereby potentially affecting the gut microbial ecosystem, highlighting the reciprocal nature of host\u2013microbiota interactions. We further examine how diet, psychosocial stress, environmental pollutants, and socioeconomic conditions may shape the microbiota\u2013epigenetic axis across diverse populations, providing a framework for understanding differences in metabolic susceptibility without attributing disparities to intrinsic biological variation. However, direct human evidence linking the gut microbiota\u2013host epigenetic axis to racial and ethnic disparities in T2DM risk remains limited, and much of the current framework is based on mechanistic studies, animal models, and associative human data rather than direct causal evidence. Further research in diverse human populations is needed to validate these pathways and establish their contribution to T2DM disparities. This framework may inform biomarker discovery, stratification, precision nutrition, and microbiome-targeted interventions and generate hypotheses for equitable prevention and personalized management of T2DM across diverse populations.<\/jats:p>","DOI":"10.3390\/nu18162668","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:04:36Z","timestamp":1786961076000},"page":"2668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Gut Microbiota\u2013Host Epigenetic Axis: An Emerging Biological Framework for Understanding Ethnic Disparities in Type 2 Diabetes Mellitus Susceptibility"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-4350","authenticated-orcid":false,"given":"Mohamed","family":"Zaiou","sequence":"first","affiliation":[{"name":"Institut Jean-Lamour, Universit\u00e9 de Lorraine, UMR 7198 CNRS, 54505 Vandoeuvre-les-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","unstructured":"NCD Risk Factor Collaboration (NCD-RisC) (2024). 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