Trimethylamine‐N‐oxide biomarker response is a function of dietary precursor intake and gut microbiota composition in healthy young men

Abstract

Trimethylamine‐N‐oxide (TMAO) has recently emerged as a novel risk factor for chronic diseases but the contribution of diet and gut microbiota to TMAO production has received limited attention. The objective of this study was to compare TMAO biomarker response to foods that contain TMAO (fish) or its dietary precursors, choline and carnitine (eggs and beef), and to determine whether TMAO response was modified by the gut microbiota. As part of a crossover feeding trial with one‐week washout intervals, healthy young men (n = 40) were randomized to study meals representing animal sources of TMAO (i.e., eggs, beef and fish) and a fruit control. Blood and urine samples were collected at baseline and throughout the 6 h study period, and a one‐time baseline stool was provided. TMAO concentrations in plasma and urine were greatly influenced by dietary precursor intake with fish yielding 50–55 times higher TMAO (P < 0.0001), 11–12 times higher trimethylamine (P < 0.0001) and 5–6 times higher dimethylamine (P < 0.0001) than eggs or beef. Notably, circulating TMAO concentrations in response to the fish study meal were increased within 15 min of consumption suggesting that TMAO itself can be absorbed without undergoing processing by the gut microbes. Analysis of 16S rRNA genes indicated that high‐TMAO producers (those with >20% increase in urinary TMAO response to eggs and beef) had more Firmicutes than Bacteroidetes (P = 0.04), and showed less richness (P = 0.03) in gut microbiota composition than low‐TMAO producers (those with <20% increase in TMAO response). Given the inverse relationship between fish consumption and heart disease, the robust increase in circulating TMAO in response to the fish study meal suggests that TMAO may not contribute to the development of heart disease in humans. In addition, TMAO response to dietary TMAO precursors (eggs and beef) appears to be dependent on the gut microbes demonstrating that TMAO may be a biomarker of the gut microbiota composition. Overall, our data raise questions about the utility of lowering circulating concentrations of TMAO, via dietary or pharmaceutical approaches, as a means to improve human health.Support or Funding InformationEgg Nutrition Center, Beef Checkoff through the National Cattlemen's Beef Association, Canadian Institutes of Health Research Postdoctoral Fellowship