Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men

Abstract

ObjectivesGut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals.DesignWe collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features.ResultsTMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO concentrations (false discovery rate <0.05). Higher habitual intake of red meat and choline was significantly associated with higher TMAO concentrations among participants who were microbial TMAO-producers (p<0.05), as characterised based on four abundant TMAO-predicting species, but not among other participants (for red meat, P-interaction=0.003; for choline, P-interaction=0.03). Among abundant TMAO-predicting species, Alistipes shahii significantly strengthened the positive association between red meat intake and HbA1c levels (P-interaction=0.01). Secondary analyses revealed that some functional features, including choline trimethylamine-lyase activating enzymes, were associated with TMAO concentrations.ConclusionWe identified microbial taxa that were associated with TMAO concentrations and modified the associations of red meat intake with TMAO concentrations and cardiometabolic risk markers. Our data underscore the interplay between diet and gut microbiome in producing potentially bioactive metabolites that may modulate cardiometabolic health.

Gut Microbiome Composition Is Predictive of Incident Type 2 Diabetes in a Population Cohort of 5,572 Finnish Adults

“…For example, C . citroniae has been positively associated with production of trimethylamine N-oxide (TMAO), which is a compound likely connected to intake of red meat ( 26 ). The direct association between red meat intake and type 2 diabetes risk has been known for >15 years ( 27 ).…”

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

“…TMA is carried through the portal circulation to the liver, where it is oxidized by the host hepatic flavin monooxygenase (FMO) to produce TMAO which is then released into circulation and eventually eliminated in the kidney (64)(65)(66). Consequently, TMAO is dependent upon dietary consumption of precursors, gut microbial enzymatic activity and host genetics (67), and may be a vital mediator among diet, gut microbiota metabolism and the risk of CRC.…”

A Dietitian-Led Vegan Program May Improve GlycA, and Other Novel and Traditional Cardiometabolic Risk Factors in Patients With Dyslipidemia: A Pilot Study

“…As vegetarians had a low baseline TMAO, and likely have, in the long-term, nurtured non-TMAO producing gut microbiota, the shift to a vegan diet did not alter their TMAO. A previous study found that nonvegetarians are ten times more likely to be high TMAO producers than vegetarians upon carnitine challenge tests, despite no difference in fasting TMAO ( 17 , 44 ) and these may be related to the presence of specific gut species ( 44 , 45 ). Collectively, these results suggest that a vegan diet may be particularly beneficial for high TMAO producers.…”