微生物组、饮食和遗传学对人血浆代谢组个体间变异的影响

2022-10-24 11:25

总之，对解释血浆代谢组个体间差异的因素进行表征，可以帮助设计调节饮食或肠道微生物组以塑造健康代谢组的方法。

SCI

22 October 2022

Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome

(IF: Nat. Med., 87.241)

Chen L, Zhernakova DV, Kurilshikov A, Andreu-Sánchez S, Wang D, Augustijn HE, Vich Vila A; Lifelines Cohort Study, Weersma RK, Medema MH, Netea MG, Kuipers F, Wijmenga C, Zhernakova A, Fu J. Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome. Nat Med. 2022 Oct 10.

Correspondence: e-mail: j.fu@umcg.nl

The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite—a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter- individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome.

人体血浆代谢组中数千种代谢物的水平受到个体遗传、饮食组成和肠道微生物组组成的强烈影响。在这里，通过评估来自荷兰的队列Lifelines DEEP和Genome的1368名广泛表型个体的1183种血浆代谢物，我们量化了血浆代谢组中由不同因素解释的个体间变异比例，分别将610、85和38种代谢物表征为与饮食、肠道微生物组和遗传学相关的主要代谢物。此外，由代谢物水平得出的饮食质量分数与饮食质量显著相关的结论，这通过详细的食物频率问卷进行评估。通过孟德尔随机化和中介分析，我们揭示了饮食、肠道微生物组和代谢物之间的假定因果关系。例如，孟德尔随机分析支持直肠真杆菌在降低血浆亚硫酸氢盐水平的潜在因果效应——亚硫酸氢盐是一种影响心血管功能的毒素。最后，基于在相隔4年的两个时间点对311名个体的血浆代谢组的分析，我们观察到代谢物水平的稳定性与该代谢物水平的变化量之间存在正相关，这可以在我们的分析中得到解释。

总之，对解释血浆代谢组个体间差异的因素进行表征，可以帮助设计调节饮食或肠道微生物组以塑造健康代谢组的方法。