Diet, Fecal Microbiome, and Trimethylamine N-Oxide in a Cohort of Metabolically Healthy United States Adults

Abstract

TMAO is elevated in individuals with cardiometabolic diseases, but it is unknown whether the metabolite is a biomarker of concern in healthy individuals. We conducted a cross-sectional study in metabolically healthy adults aged 18–66 years with BMI 18–44 kg/m2 and assessed the relationship between TMAO and diet, the fecal microbiome, and cardiometabolic risk factors. TMAO was measured in fasted plasma samples by liquid chromatography mass spectrometry. The fecal microbiome was assessed by 16S ribosomal RNA sequencing and recent food intake was captured by multiple ASA24 dietary recalls. Endothelial function was assessed via EndoPAT. Descriptive statistics were computed by fasting plasma TMAO tertiles and evaluated by ANOVA and Tukey’s post-hoc test. Multiple linear regression was used to assess the relationship between plasma TMAO and dietary food intake and metabolic health parameters. TMAO concentrations were not associated with average intake of animal protein foods, fruits, vegetables, dairy, or grains. TMAO was related to the fecal microbiome and the genera Butyribrio, Roseburia, Coprobaciullus, and Catenibacterium were enriched in individuals in the lowest versus the highest TMAO tertile. TMAO was positively associated with α-diversity and compositional differences were identified between groups. TMAO was not associated with classic cardiovascular risk factors in the healthy cohort. Similarly, endothelial function was not related to fasting TMAO, whereas the inflammatory marker TNF-α was significantly associated. Fasting plasma TMAO may not be a metabolite of concern in generally healthy adults unmedicated for chronic disease. Prospective studies in healthy individuals are necessary.

TMAO and its precursors in relation to host genetics, gut microbial composition, diet, and clinical outcomes: Meta-analysis of 5 prospective population-based cohorts

“…9, 21, 55 Taken together with our results, these findings suggest that circulating TMAO may not be a metabolite of concern in individuals from the general population. 9, 17, 21, 55…”

“…14, 15, 16, 74 In our study population, no association was found between TMAO and eggs or red meat. 21 Fish and seafood are rich in TMAO and TMA and they can be directly absorbed without being transformed by gut microbiota. 14 As previous studies linked TMAO to atherosclerosis and CVD, these findings might be contra intuitive as fish is generally accepted to be cardioprotective.…”

“…Association studies point to several genera, however, published results are in most cases heterogeneous among studies. 12, 17, 18, 19, 20, 21 On the other hand, several studies have focused on identifying microbial genomes harboring the metabolic potential to produce TMA. 22, 23 Even though, Proteobacteria and Firmicutes phyla had the most predicted TMA-production potential, 23 reports suggest that there is no association between gene abundance levels and TMAO plasma concentrations.…”

Atherosclerosis and trimethylamine-N-oxide — the gut microbiota potential

“…Определены бактерии, синтезирующие ТМАО: тип Firmicutes (роды Anaerococcus, Clostridium, Enterococcus, Streptococcus, Desulfovibrio, Eubacterium), тип Proteobacteria (Enterobacter, Escherichia, Klebsiella, Proteus, Actinobacter, Citrobacter), тип Actinobacteria (Mobiluncus, Olsenella) и тип Bacteroidetes (Bacteroides) [16,27]. Напротив, у метаболически здоровых взрослых первый терциль концентрации ТМАО в плазме крови натощак был обогащен родами Roseburia, Butyrivibrio, Coprobacillus и Catenibacterium по сравнению с третьим терцилем [30]. Firmicutes, как правило, содержат ТМА-генерирующий кластер генов, утилизирующих холин [16], что идентифицировали метагеномные скрининги [30].…”

“…Напротив, у метаболически здоровых взрослых первый терциль концентрации ТМАО в плазме крови натощак был обогащен родами Roseburia, Butyrivibrio, Coprobacillus и Catenibacterium по сравнению с третьим терцилем [30]. Firmicutes, как правило, содержат ТМА-генерирующий кластер генов, утилизирующих холин [16], что идентифицировали метагеномные скрининги [30].…”