BGI-Shenzhen, Shenzhen, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Nat Genet. 2022 Jan;54(1):52-61. doi: 10.1038/s41588-021-00968-y. Epub 2022 Jan 3.
The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization analyses on 3,432 Chinese individuals with whole-genome, whole-metagenome, anthropometric and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate and selenium. Two-sample Mendelian randomization with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.
肠道微生物组与多种生理状态有关，但因果关系仍存在争议。在这里，我们对 3432 名具有全基因组、全宏基因组、人体测量和血液代谢特征数据的中国人进行了双向孟德尔随机化分析。我们确定了肠道微生物组与血液代谢物之间的 58 种因果关系，并复制了其中的 43 种。粪便 Oscillibacter 和 Alistipes 的相对丰度增加与甘油三酯浓度降低有关。相反，谷氨酸等血液代谢物似乎会降低粪便 Oxalobacter，而 Proteobacteria 的成员则受到 5-甲基四氢叶酸、丙氨酸、谷氨酸和硒等代谢物的影响。来自日本生物银行的两样本孟德尔随机化分析部分证实了与甘油三酯和尿酸的结果，并为癌症和心血管疾病的粪便细菌标志物提供了因果支持。本研究说明了人类遗传信息的价值，有助于优先考虑肠道微生物特征进行机制和临床研究。
