Cross-Cultural Nutritional Epigenomics: Diet and Microbiome Interactions Shaping Type 2 Diabetes in Arab and Western...

In the Middle East and North Africa (MENA) region, the prevalence of Type 2 Diabetes (T2D) is 17-18%, substantially higher than the ~9-10% reported in Western populations, with some Gulf states approaching 25% in adults. Historically, Arab diets, characterized by high fiber intake from whole grains, legumes, and fermented dairy products, have contrasted markedly with the Western dietary pattern increasingly prevalent among urbanized Arab populations. These nutritional shifts have been associated with changes in gut microbial composition, including lower representation of short-chain fatty acid-producing bacteria and higher abundance of dysbiosis-associated taxa. Concurrently, diet-derived compounds and microbial metabolites have been associated with changes in DNA methylation, histone modifications, and non-coding RNA expression. Epigenome-wide association studies revealed both shared and population-specific methylation signatures in patients with T2D. However, integrated multi-omics studies remain limited in Arab populations, where the disease burden is highest. This review integrates emerging evidence on diet-linked epigenetic alterations, microbiome-associated metabolic pathways, and their intersection in potentially contributing to T2D risk and progression. Given the heterogeneity of T2D across populations, there is a pressing need for culturally contextualized precision medicine frameworks that integrate population-specific diet-microbiome-epigenome dynamics rather than extrapolating findings across populations. Additionally, this review synthesizes evidence that dietary patterns are associated with T2D-relevant pathways through the diet-microbiome-epigenome axis, with emphasis on Arab/MENA populations and Western comparator cohorts.