Fig. 3: Modest impact of diet and microbiota composition on circulating TMAO in BMIS MetaCardis subjects.

A Associations between circulating TMAO and its precursors with habitual consumption of food items rich in TMAO precursors (N = 763; left panel) or with its precursors themselves (right panel). B Principal coordinates analysis of Bray–Curtis dissimilarity matrices of participants (N = 834) stratified in TMAO clusters by the k-means algorithm (1 the lowest, 4 the highest) at the species level (input; 699 species present in at least 20% of the BMIS population). Insert; PERMANOVA (999 iterations) of taxonomic Bray–Curtis dissimilarity matrices association with regularized TMAO levels with age, sex, and country of recruitment as covariates. C Overlap of microbiome taxa significantly associated with circulating TMAO (Spearman partial correlations adjusted for age, sex country of recruitment and BMI) and the consumption of food items rich in TMAO precursors in BMIS participants (N = 763). D Volcano plot of differential bacterial species abundances between BMIS participants in the lowest (N = 101) and highest (N = 147) TMAO clusters (blue; taxa significantly depleted, red; taxa significantly enriched in the high TMAO cluster respectively, two-sided Mann–Whitney U test, pFDR<0.05). E Venn diagram summarizing the overlap between taxa associating with circulating TMAO according to our three complimentary analyses (SPC Spearman correlations, ML machine learning and feature attribution analysis; MU: two-sided Mann–Whitney U test between high and low TMAO clusters). For all *pFDR <0.05, **pFDR <0. 0.01. Source data are provided as a Source Data file.