Erythrocyte n-6 polyunsaturated fatty acids, gut microbiota and incident type 2 diabetes: a prospective cohort study

Miao, Z.; Lin, J.-s.; Mao, Y.; Chen, G.-d.; Zeng, F.-f.; Dong, H.-l.; Jiang, Z.; Wang, J.; Xiao, C.; Shuai, M.; Gou, W.; Fu, Y.; Imamura, F.; Chen, Y.-m.; Zheng, J.-S.

Objective: To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes (T2D) and explore the potential role of gut microbiota in the association. Design: We evaluated 2,731 non-T2D participants recruited between 2008-2013 in the Guangzhou Nutrition and Health Study, China. T2D cases were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n=1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident T2D, and diversity and composition of gut microbiota. Results: Over 6.2 years of follow-up, 276 T2D cases were identified (risk=0.10). Higher levels of erythrocyte {gamma}-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher T2D incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% confidence intervals: 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (-diversity, both p<0.05) during follow-up, and significantly associated with microbiota {beta}-diversity (p=0.002). Seven genera ( Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA, and in participants without T2D. Conclusion: Relative concentrations of erythrocyte GLA were positively associated with incident T2D in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and T2D etiology.