Association Among Long-chain Polyunsaturated Fatty Acids,Gut Microbiota And Disorders Of Glucose And Lipid Metabolism And Related Mechanism

The associations between polyunsaturated fatty acids(PUFA)and metabolic disorders,such as type 2 diabetes and hyperlipidemia have been controversial.In particular,prospective evidence from the Chinese population is limited.Gut microbiota and furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid(CMPF)may play the important role linking PUFA and type 2 diabetes.Gene-diet interaction potentially help interpret the inconsistent results between PUFA and metabolic disorders.In the present thesis,we examined the prospective association of n-6 PUFA with incident type 2 diabetes in a Chinese population.We found that higher levels of erythrocyte γ-linolenic acid(GLA),but not linoleic acid or arachidonic acid,were associated with higher type 2 diabetes incidence.In order to explore the potential role of gut microbiota in the above association,we examined the association of n-6 PUFA and related food sources with gut microbiota in the human cohort.We found that baseline GLA was inversely associated with gut microbial richness and diversity(α-diversity)during follow-up,and significantly associated with microbiota β-diversity.Microbial α-diversity acted as a potential mediator in the association between GLA and type 2 diabetes.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.Short-term intake of vegetable oils was positively associated with gut microbial α-diversity.Long-term nuts consumption had an inverse association with Enterococcaceae spp,which was positively associated with fasting insulin.We then investigated the association among n-3 PUFA,CMPF and type 2 diabetes in a prospective cohort.We found that erythrocyte eicosapentaenoic acid(EPA),docosapentaenoic acid(DPA)and docosahexaenoic acid(DHA)were positively associated with CMPF.CMPF was inversely associated with type 2 diabetes and glycemic traits.Erythrocyte EPA and DPA had inverse associations with incident type2 diabetes.CMPF may act as a potential mediator in the above associations.Animal study indicated that n-3 PUFA could increase the serum CMPF and taxa in Clostridiales.In addition,gut microbiota could modulate the increase of CMPF stimulated by the EPA and DHA.At last,we evaluated the CD36-marine n-3 PUFAs interaction on blood lipids and gut microbiota in several human cohorts.We found that CD36 rs1527483-GG carriers responded better to high marine n-3 PUFA exposure with higher blood high-density lipoprotein cholesterol and lower triglycerides.We identified DHA as the driven individual marine n-3 PUFA biomarker,which showed interaction with CD36rs1527483.Among the rs1527483-GG carriers,but not other genotype groups,DHA exposure was positively associated with bacterial α-diversity,taxa in Clostridiales,and fecal propionic acid levels.The identified microbial features were correlated with blood lipids,and the host biosynthesis and metabolism pathways of bile acids and aromatic amino acids.In conclusion,we found that n-6 PUFA was associated with higher risk of type 2diabetes,while n-3 PUFA was associated with lower risk of type 2 diabetes in the Chinese populations.Gut microbiota and CMPF may mediate the association between PUFA and type 2 diabetes.Animal study suggested that the increase of CMPF may be driven by the EPA and DHA intervention potentially via gut microbiota.Gene-fatty acid interaction modulated the blood lipids and gut microbiota.These findings contribute to the development of precision nutrition strategy for the prevention and treatment of glucose and lipid-related metabolic disorders.