Abstract P507: Interplay Between Diet and Gut Microbiota, and Circulating Levels of Trimethylamine N-oxide: Findings From the Men’s Lifestyle Validation Study

Background: Trimethylamine N-oxide (TMAO) is proposed as a possible culprit linking red meat intake and poor cardiovascular health. The relationship between diet, microbial metabolism, circulating TMAO levels, and cardiometabolic health in free-living individuals, is yet to be elucidated. Hypothesis: Specific microbial taxa may modulate associations of choline/L-carnitine and red meat intake with plasma TMAO levels and cardiometabolic traits. Method: We collected 2 pairs of fecal samples (n=925) and, simultaneously, 2 blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study in 2012. We performed Shotgun metagenomic sequencing using fecal samples and identified microbial taxonomic features using MetaPhlAn2. We measured hemoglobin A1c (HBA1c), and plasma levels of TMAO, lipids, and other cardiometabolic risk markers. Diet was assessed repeatedly using validated food-frequency questionnaires and dietary records. Results: Multivariable random-effect linear regressions identified 10 bacterial species that were significantly associated with TMAO levels ( FDR <0.05; Figure A ), and these species significantly modified the associations of dietary choline/L-carnitine and/or red meat intake with TMAO levels ( P interaction <0.05). In particular, Alistipes s hahii and Clostridium c itroniae significantly strengthened the association between red meat intake and TMAO levels, whereas Eubacterium b iforme attenuated this association ( P interaction <0.05). Consistently, the associations of higher red meat intake with higher HBA1c and lower high-density lipoprotein cholesterol levels were more pronounced in the presence of A. s hahii and C. c itroniae or in the absence of E. b ifome ( Figure B ). Conclusions: We identified microbial taxa that modify the associations of red meat intake with circulating TMAO levels and cardiometabolic traits, in free-living men, suggesting an interplay between diet and microbial metabolism in producing TMAO and affecting cardiometabolic health.