Type 2 diabetes-associated gut microbial composition and short chain fatty acids differ across the epidemiologic...

The gut microbiota and microbially produced short chain fatty acids (SCFAs) are increasingly linked to type 2 diabetes (T2D), particularly in the context of dietary transitions from fiber-rich to more ultra-processed foods. Data in African origin populations are lacking. We examined the cross-sectional relationships between the gut microbiota, SCFAs, and T2D by performing amplicon sequencing and targeted metabolomics from fecal samples and measuring fasting glucose, insulin, and C-peptide in 1505 African origin middle-aged adults from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbial diversity and SCFAs were highest among Ghanaian and lowest among US participants. T2D was associated with lower microbial diversity, but not when stratifying by site. Differential abundance analysis (adjusted for site, sex, BMI, and age) identified microbes associated with T2D: Romboutsia was negatively associated with T2D, while positively associated taxa included Escherichia-Shigella sp., Dielma fastidiosa, Klebsiella, and Bacteroides vulgatus. Several species that were differentially abundant by T2D showed strong correlations with SCFA concentrations, although the significance varied by site. Our results suggest that associations between the gut microbiota, SCFAs, and T2D may differ by environmental, dietary, and ecological contexts. Amid the shifting global dietary patterns, further research is needed to inform gut microbiota-targeted approaches to address the global T2D burden.