The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex h
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RESEARCH
Open Access
The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases Fengzhe Xu1†, Yuanqing Fu1,3†, Ting-yu Sun2, Zengliang Jiang1,3, Zelei Miao1, Menglei Shuai1, Wanglong Gou1, Chu-wen Ling2, Jian Yang4,5, Jun Wang6*, Yu-ming Chen2* and Ju-Sheng Zheng1,3,7*
Abstract Background: Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. Results: This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. Conclusions: These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans. Keywords: Gut microbiome, Host genetics, Bidirectional Mendelian randomization analyses, Disease-microbiome features
* Correspondence: [email protected]; [email protected]; [email protected] † Fengzhe Xu and Yuanqing Fu contributed equally to the work. 6 CAS Key Laboratory for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China 2 Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China 1 Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Crea
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