Host–microbial co-metabolism products are being increasingly recognised 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 NMR 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, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini–Hochberg, 10 % false discovery rate). 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 (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven 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.

人们越来越认识到宿主-微生物共代谢产物在生理过程中发挥重要作用。然而，采用综合方法考虑宿主-微生物代谢关系的研究仍然很少。代谢组学分析产生有关在给定生物隔间中发现的代谢物的详细信息，为这种方法提供了希望。这项工作旨在探索Milieu Intérieur研究的健康成人中宿主血浆代谢组学特征与肠道微生物群组成之间的关联。对于 846 名受试者，通过对粪便中的 16S rRNA 基因进行测序来分析肠道微生物群组成。通过血浆的质子核磁共振分析产生代谢组学特征。代谢组学变量与α之间的关联- 和β -多样性指数和相对分类群丰度分别使用多重调整的部分 Spearman 相关性、置换方差分析和线性模型的多变量关联进行了测试。应用了多重测试校正（Benjamini-Hochberg，10% 的错误发现率）。微生物丰富度与脂质相关信号呈负相关，与氨基酸、胆碱、肌酐、葡萄糖和柠檬酸盐呈正相关（-0·133 ≤ Spearman's ρ ≤ 0·126）。检测到代谢组学信号与类群丰度之间的特定关联（属水平有 25 个，物种水平有 19 个）：值得注意的是，观察到肌酐的许多关联（与 11 个物种呈正相关，与粪杆菌 prausnitzii )。这项基于人群的大规模研究突出了与肠道微生物特征相​​关的代谢物，并为理解复杂的宿主-肠道微生物群代谢关系提供了新的见解。特别是，我们的结果支持“肠-肾轴”的含义。需要更多的研究来详细探索这些复杂的相互作用及其对宿主健康的影响。