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

Abstract

Abstract Objectives To examine the prospective association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes (T2D), and the potential role of gut microbiota. Methods 2731 non-T2D participants recruited between 2008–2013 in the Guangzhou Nutrition and Health Study were included in the present study. 276 incident T2D was ascertained after a median follow-up of 6.2 years, and 16S rRNA profiling was conducted using stool samples collected during follow-up. We examined the prospective association of erythrocyte n-6 PUFA biomarkers with incident T2D, and with diversity and composition of gut microbiota. Results Higher levels of erythrocyte γ-linolenic acid (GLA) were associated with higher T2D risk, with relative risk (quartile 4 versus 1) 1.72 (95% confidence intervals: 1.21, 2.44), adjusting for potential confounders. No association with T2D was found for erythrocyte linoleic acid or arachidonic acid. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up, and significantly associated with microbiota β-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. Conclusions The present study suggests that erythrocyte GLA biomarker is positively associated with incident T2D in a Chinese population. High GLA status is associated with unfavorable gut microbial profiles, which may contribute to the increased risk of T2D. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and T2D etiology. Funding Sources This study was funded by the National Natural Science Foundation of China, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.