Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance.

ABSTRACT

Recent findings have shown an inverse association between circulating C150/C170 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C150/C170 diet dose response study. Endogenous production was assessed through a stearic acid infusion, phytol supplementation, and a Hacl1-/- mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C150/C170 with the prognosis of glucose intolerance. We found that circulating C150/C170 levels were not influenced by the gut-microbiota. The dose response study showed C150 had a linear response, however C170 was not directly correlated. The phytol supplementation only decreased C170. Stearic acid infusion only increased C170. Hacl1-/- only decreased C170. The glucose intolerance study showed only C170 correlated with prognosis. To summarise, circulating C150 and C170 are independently derived; C150 correlates directly with dietary intake, while C170 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C170 and recognizing its link with metabolic disease.