Dietary factors, gut microbiota, and serum trimethylamine-N-oxide associated with cardiovascular disease

Abstract

Background Trimethylamine-N-oxide (TMAO), a diet-derived and gut microbiota-related metabolite, is associated with cardiovascular disease (CVD). However, the major dietary determinants and the specific gut bacterial taxa related to TMAO remain to be identified in humans. We aimed to identify dietary and gut microbial factors independently and jointly associated with circulating TMAO. Results We examined usual dietary intake, fecal gut microbiome profiled by shotgun metagenomics, and their interactions in relation to serum TMAO and its precursors among up to 3972 adult participants from the Hispanic Community Health Study/Study of Latinos. We confirmed the positive association between TMAO and prevalent CVD (OR = 1.28, P = 4.36⋅10− 4). Fish (P = 1.26⋅10− 17), red meat (P = 3.33⋅10− 16), and egg (P = 3.89⋅10− 5) intakes were top dietary factors positively associated with serum TMAO independently of each other. Red meat and egg intakes, but not fish intake, were positively associated with serum TMAO precursors (e.g., carnitine, choline). We identified 9 gut bacterial species significantly associated with serum TMAO after multiple testing correction (FDR < 0.05). All 4 TMAO-positively-associated bacteria belong to the Clostridiales order, 3 of which may have homologous genes encoding carnitine monooxygenase, an enzyme converting carnitine to trimethylamine (TMA)/TMAO. The red meat-TMAO association was more pronounced for participants with higher abundance of these 4 bacterial species than those with lower abundance (Pinteraction=0.013), but such microbial modification was not observed for fish-TMAO or egg-TMAO associations. Conclusion In US Hispanics/Latinos, fish, red meat, and egg intakes are major dietary factors associated with serum TMAO. The identified potential TMA-producing gut microbiota and microbial modification on the red meat-TMAO association support microbial TMA/TMAO production from dietary carnitine, while the fish-TMAO association is independent of gut microbiota.

Effects of Lean Pork on Microbiota and Microbial‐Metabolite Trimethylamine‐N‐Oxide: A Randomized Controlled Non‐Inferiority Feeding Trial Based on the Dietary Guidelines for Americans

“…The findings align with existing observational data suggesting that a broad and consistent red meat-TMAO connection may not exist. [53][54][55][56] A similar TMAO response to pork and chicken is likely due to both proteins containing precursors for microbial TMA production. Although betaine, choline, and L-carnitine contents were slightly different between the two intervention proteins, a similar level of abundance in the blood reflects not only dietary intakes but also endogenous productions and tight homeostatic regulations.…”