Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical studies.To gain insight into the interactions between host genetic varia...Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical studies.To gain insight into the interactions between host genetic variation and the gut microbiome,we analyzed both the human genome and gut microbiome collected from a cohort of 190 students in the same boarding college and representing 3 ethnic groups,Uyghur,Kazakh,and Han Chinese.We found that differences in gut microbiome were greater between genetically distinct ethnic groups than those genetically closely related ones in taxonomic composition,functional composition,enterotype stratification,and microbiome genetic differentiation.We also observed considerable correlations between host genetic variants and the abundance of a subset of gut microbial species.Notably,interactions between gut microbiome species and host genetic variants might have coordinated effects on specific human phenotypes.Bacteroides ovatus,previously reported to modulate intestinal immunity,is significantly correlated with the host genetic variant rs12899811(meta-P=5.55×10^(-5)),which regulates the VPS33B expression in the colon,acting as a tumor suppressor of colorectal cancer.These results advance our understanding of the micro-coevolution of the human gut microbiome and their interactive effects with host genetic variation on phenotypic diversity.展开更多
基金the National Natural Science Foundation of China(NSFC)(31771388,32030020,31525014,32071465,31871334,31671374,91731303,31961130380,and 32041008)the Strategic Priority Research Program(XDPB17,XDB38000000)+2 种基金the Chinese Academy of Sciences,National Key Research and Development Program of China(2018YFC0910502,2016YFC0906403)the UK Royal Society-Newton Advanced Fellowship(NAF\R1\191094)the Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical studies.To gain insight into the interactions between host genetic variation and the gut microbiome,we analyzed both the human genome and gut microbiome collected from a cohort of 190 students in the same boarding college and representing 3 ethnic groups,Uyghur,Kazakh,and Han Chinese.We found that differences in gut microbiome were greater between genetically distinct ethnic groups than those genetically closely related ones in taxonomic composition,functional composition,enterotype stratification,and microbiome genetic differentiation.We also observed considerable correlations between host genetic variants and the abundance of a subset of gut microbial species.Notably,interactions between gut microbiome species and host genetic variants might have coordinated effects on specific human phenotypes.Bacteroides ovatus,previously reported to modulate intestinal immunity,is significantly correlated with the host genetic variant rs12899811(meta-P=5.55×10^(-5)),which regulates the VPS33B expression in the colon,acting as a tumor suppressor of colorectal cancer.These results advance our understanding of the micro-coevolution of the human gut microbiome and their interactive effects with host genetic variation on phenotypic diversity.