Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota, and Incident Type 2 Diabetes: A Prospective Cohort Study.

Abstract

To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association. We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (<i>n</i> = 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 type 2 diabetes and diversity and composition of gut microbiota. Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both <i>P</i> < 0.05) during follow-up and significantly associated with microbiota β-diversity (<i>P</i> = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (<i>P</i> < 0.05). Seven genera (<i>Butyrivibrio</i>, <i>Blautia</i>, <i>Oscillospira</i>, <i>Odoribacter</i>, <i>S24-7 other</i>, <i>Rikenellaceae other</i>, and <i>Clostridiales other</i>) were enriched in quartile 1 of GLA and in participants without type 2 diabetes. Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes 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 type 2 diabetes etiology.