Ethnicity-matched case-control study reveals significant gut microbiota differences in Malaysian adults with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a major global health issue projected to exceed 700 million cases by 2045. In Malaysia, T2DM prevalence has risen, with notable ethnic disparities. The gut microbiota's role in T2DM pathogenesis is well recognized, yet its composition in Malaysia's ethnically diverse population remains underexplored. This study aimed to characterize gut microbiota composition among T2DM and ethnicity-matched adults without diabetes (nonDM) in Malaysia. A case-control study was conducted with 45 T2DM and 45 nonDM participants matched by ethnicity from a primary care clinic in Klang Valley, Malaysia. Faecal DNA was subjected to 16S rRNA sequencing to identify microbiota diversity and composition differences and compare predicted functional capabilities. Correlations between bacterial taxa, clinical characteristics and dietary intake were analysed. T2DM participants showed decreased alpha diversity (observed, -value=0.002, =0.69; Shannon, -value<0.001, =0.73) and significant differences in beta diversity (permutational multivariate ANOVA, ²=0.036, -value=0.001). Linear discriminant analysis effect size and multiple regression analysis, adjusted for covariates age, gender, BMI and intakes of protein, fat, carbohydrate and fibre, identified the phylum and genera to be increased, while the genera and decreased in T2DM. These bacteria were associated with various clinical characteristics and dietary intake. However, these 'potential biomarkers' were not uniformly present across all participants, suggesting that individual bacterial taxa may not serve as universal biomarkers. Significant gut microbiota differences exist between T2DM and nonDM individuals in Malaysia, indicating a dysbiosis characterized by increased pro-inflammatory bacteria and reduced short-chain fatty acid-producing bacteria in T2DM. While these findings highlight the potential functional relevance of gut microbiota in T2DM pathogenesis, addressing limitations such as participant matching for confounding factors in future studies could uncover additional significant differences in microbiota composition. Furthermore, the variability in taxa prevalence across individuals suggests that targeting microbial metabolic products may offer more promising strategies to inform microbiota-targeted interventions than relying solely on specific bacterial taxa as biomarkers.