Abstract 13063: Gut Microbiota-Derived Metabolites and Cardiometabolic Traits: Findings From a Monozygotic Twin Study

Abstract

Introduction: Microbial metabolites are small chemical compounds produced by gut microbiota when it breaks down food, chemicals, or other environmental exposures. These metabolites serve as signaling molecules between the host and gut microbiota and regulate numerous aspects of host physiology, immunity, and metabolism. Hypothesis: Gut dysbiosis is associated with cardiometabolic disorders via alterations in microbial metabolites. Aims: To identify gut-microbiota-derived metabolites associated with cardiometabolic traits. Methods: Using hydrophilic interaction liquid chromatography (HILIC), we measured the relative abundances of 62 food and gut-microbiota-derived metabolites in plasma sample of 46 complete monozygotic twin pairs (34 female-female pairs, 12 male-male pairs, mean age 36.2) enrolled in the Mood and Methylation Study (MMS), an observational study designed to identify biomarkers associated with depressive symptoms using a twin design. Information for cardiometabolic traits, including body mass index, waist circumference, blood glucose, HbA1c, insulin, triglycerides, total cholesterol, HDL and LDL, was collected using standard questionnaires or laboratory methods. The association of each metabolite with cardiometabolic trait was examined by a linear mixed-effects model, adjusting for age, sex, smoking, drinking, and depressive symptoms. The co-twin correlation was accounted for by including twin pair as a random effect in the model. Results: After correction for multiple testing by false discovery rate (FDR<0.05), 15 microbial metabolites were significantly associated with one or more cardiometabolic traits. Of these, 7 glycerophospholipids (e.g., PC(32:1), PC(34:4), PE(38:6)) and 2 sphingomyelins (i.e., SM(d36:1), SM(d36:2)) were positively, whereas betaine, creatinine, urea, pipecolic acid, N1, N12-diacetylspermine, and 3-chloro-L-tyrosine were negatively associated with LDL, triglycerides, total cholesterol, and HbA1c. Conclusions: Our results revealed novel microbial metabolites associated with cardiometabolic traits and support their potentially important role in mediating the interactions between gut microbiota and host pathophysiology.