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

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posted on 28.07.2020 by Zelei Miao, Jie-sheng Lin, Yingying Mao, Geng-dong Chen, Fang-fang Zeng, Hong-li Dong, Zengliang Jiang, Jiali Wang, Congmei Xiao, Menglei Shuai, Wanglong Gou, Yuanqing Fu, Fumiaki Imamura, Yu-ming Chen, Ju-Sheng Zheng
OBJECTIVE 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.

RESEARCH DESIGN AND METHODS We evaluated 2,731 participants without type 2 diabetes recruited between 2008-2013 in the Guangzhou Nutrition and Health Study, China. Type 2 diabetes 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 type 2 diabetes, and diversity and composition of gut microbiota.

RESULTS Over 6.2 years of follow-up, 276 type 2 diabetes cases 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% confidence intervals: 1.21, 2.44) adjusted for potential confounders. 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). α-diversity acted as a potential mediator in the association between GLA and type 2 diabetes (p<0.05). 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 type 2 diabetes.

CONCLUSIONS 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.

Funding

This study was funded by the National Natural Science Foundation of China (81903316, 81773416), Zhejiang Ten-thousand Talents Program (101396522001), Westlake University (101396021801) and the 5010 Program for Clinical Researches (2007032) of the Sun Yat-sen University (Guangzhou, China). The funder had no role in study design, data collection and analysis, decision to publish, or writing of the manuscript.

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