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

1. BGI-Shenzhen, Shenzhen, China.
Authors
Liu X¹
Tong X¹
Zou Y¹
Lin X¹
Zhao H¹
Tian L¹
Jie Z¹
Wang Q¹
Zhang Z¹
Xiao L¹
Qiu X¹
Zi J¹
Wang R¹
Xu X¹
Yang H¹
Wang J¹
Zong Y¹
Liu W¹
Hou Y¹
Zhu S¹
Jia H¹
Zhang T¹
(22 authors)
2. China National Genebank, BGI-Shenzhen, Shenzhen, China.
Authors
Lu H²
(1 author)

ORCIDs linked to this article

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Nature Genetics, 03 Jan 2022, 54(1):52-61
https://doi.org/10.1038/s41588-021-00968-y PMID: 34980918

This article is based on a previously available preprint.

Abstract

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.

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Read article at publisher's site: https://doi.org/10.1038/s41588-021-00968-y

Read article for free, from open access legal sources, via Unpaywall: https://www.biorxiv.org/content/biorxiv/early/2021/10/18/2020.06.30.181438.full.pdf

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

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Authors

ORCIDs linked to this article

Abstract

Full text links

References

Metagenome-wide association studies: fine-mining the microbiome.

Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations.

Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity.

Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.

A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases.

The effect of host genetics on the gut microbiome.

Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.

Association of host genome with intestinal microbial composition in a large healthy cohort.

Host genetic variation impacts microbiome composition across human body sites.

Environment dominates over host genetics in shaping human gut microbiota.

Citations & impact

Impact metrics

Citations of article over time

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Article citations

Causal Relationship Between Gut Microbiota, Metabolites, and Sarcopenia: A Mendelian Randomization Study.

Hyperuricemia and its related diseases: mechanisms and advances in therapy.

Probiotic Potential of Lactobacillus and Enterococcus Strains Isolated From the Faecal Microbiota of Critically Endangered Hangul Deer (Cervus hanglu hanglu): Implications for Conservation Management.

Unveiling the association between HMG-CoA reductase inhibitors and bladder cancer: a comprehensive analysis using Mendelian randomization, animal models, and transcriptomics.

Causal role of blood metabolites in HER-positive and HER-negative breast cancer: a Mendelian randomization (MR) study.

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