Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults
Résumé
Host-microbial co-metabolism products are being increasingly recognized to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host-microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton nuclear magnetic resonance analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, PERMANOVAs, and MaAsLins, respectively. A Multiple testing correction was applied (Benjamini-Hochberg, 10%-FDR). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose, and citrate (-0.133 ≤ Spearman's ρ ≤ 0.126). Specific associations between metabolomic signals and abundances of taxa were detected (25 at the genus level and 19 at the species level): notably, numerous associations were observed for creatinine (positively associated with 11 species, and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host-gut microbiota metabolic relationships. In particular, our results support the implication of a "gut-kidney axis". More studies providing a detailed exploration of these complex interactions, and their implications for host health are needed.
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