(P20-003-23) Differences in Predictive Functional Pathways of Gut Microbiota of High and Low Trimethylamine Oxide Producers in Adults Aged 35–64 Years

Objectives: The primary objective of this study was to identify gut bacteria metabolic pathways associated with high and low levels of trimethylamine oxide (TMAO) in adults with at least one risk factor for cardiovascular disease.

Methods: This was a cross-sectional analysis of data generated from a clinical trial (NCT04887662) that assessed the effects of fermented vegetables on the gut bacteria and markers of inflammation in adults aged 35 to 64 years. Plasma TMAO levels were measured in 84 participants by enzyme-linked immunosorbent assay and dietary intake was assessed via a 24-hour recall. Stool samples from participants with the six highest (high producers) and lowest levels of TMAO (low producers) were sequenced and the data were input into PICRUSt2 for prediction of microbial functional pathways. Mann-Whitney tests were performed to compare dietary variables between groups.

Results: Median levels of TMAO were 247.8 ng/mL and 1358.5 ng/mL for the low and high producers, respectively. There were no differences in calorie, protein or choline intake between the two groups. There were 24 bacterial pathways that were significantly different between the two groups. Pathways upregulated in high TMAO producers compared with low producers were related to arginine (P < 0.03), thiamin (P=0.0012), heme (P=0.039), and methione biosynthesis (P=0.048), and acetylneuraminate catabolism (P=0.023). On the other hand, low TMAO producers showed upregulation of nucleoside/nucleotide biosynthesis and fermentation pathways. Although it is not clear whether the identified pathways are associated with synthesis of TMAO, it is noteworthy that acetylneuraminate can be fermented by oral bacteria that may enter the bloodstream via dental caries and cause infections and more serious conditions such as endocarditis.

Conclusions: High TMAO producers showed upregulation of metabolic pathways involved in arginine, methionine and thiamin synthesis while low TMAO producers showed upregulation of nucleotide biosynthesis and fermentation pathways. It remains to be determined whether these differences in microbial pathways between high and low TMAO producers are relevant to produce the TMAO precursor, trimethylamine, by the gut microbiota.

Funding Sources: This research was supported by the Mackenzie Foundation.