Associations between rmn plasma metabolomic profiles and gut microbiota composition in a healthy French adult population

Introduction and purpose of the study: Host-microbiotic co-metabolism is at the origin of a very large number of molecules integrated within complex metabolic axes. Many studies have focused on the specific functional characterization of some of these molecules (AGCC, BCAA, TMAO, etc.), but studies looking more generally at metabolic relationships between the host and its gut microbiota remain rare. As such, the global study of endogenous and exogenous metabolites present in plasma by non-targeted metabolomics seems promising. The objective of this study was to characterize associations between plasma metabolomic profiles and gut microbiota composition in a healthy adult population. Material and methods: The composition of the gut microbiota was determined in the stool (sequencing of the 16S rRNA gene, the Jaccard and Bray-Curtis matrices were determined) and the metabolomic profiles were generated using the CPMG and NOESY NMR sequences on plasma samples, in 846 individuals of the population Internal Medium. The overall co-structure of 16S and NMR data was evaluated by co-inertia. Associations between metabolomic variables on the one hand and matrices of β-diversity or abundance of taxa on the other hand were calculated by PERMANOVA or MaAsLin adjusted for sex, age, BMI, smoking status and activity. physical (PERMANOVA also adjusted to the depth of sequencing). A Benjamini-Hochberg correction (FDR-10%) was applied. Results and Statistical Analysis: Overall co-inertia of microbiota and metabolomic data was limited ( RV ≤ 0.05). In contrast, specific associations were detected. The Jaccard and Bray-Curtis matrices were significantly and respectively associated with 51 and 3 CPMG variables, some of which have already been identified (pyruvate, tyrosine, choline, glucose, etc.). Associations between pyruvate and 3 bacterial genera (positive with Catabacter and Acholeplasma, negative with Faecalibacterium ) were highlighted. Analysis of associations between NOESY metabolomic variables and 16S microbiota data, and the identification of discriminant metabolites are ongoing. Conclusion: These preliminary results make it possible to demonstrate associations between the NMR metabolomic profile determined on the host plasma and the composition of the intestinal microbiota. However, this study does not conclude on a potential causal relationship, and further studies are needed.