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Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome

By Xiaomin Liu, Xin Tong, Yuanqiang Zou, Xiaoqian Lin, Hui Zhao, Liu Tian, Zhuye Jie, Qi Wang, Zhe Zhang, Haorong Lu, Liang Xiao, Xuemei Qiu, Jin Zi, Rong Wang, Xun Xu, Huanming Yang, Jian Wang, Yang Zong, Weibin Liu, Yong Hou, Shida Zhu, Huijue Jia, Tao Zhang

Posted 01 Jul 2020
bioRxiv DOI: 10.1101/2020.06.30.181438

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization (MR) 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 MR 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.

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