Fecal microbiota transplantation(FMT)of human fecal samples into germ-free(GF)mice is useful for establishing causal relationships between the gut microbiota and human phenotypes.However,due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms,it may not be possible to replicate human phenotypes in mice through FMT;similarly,treatments that are effective in mouse models may not be effective in humans.In this study,we aimed to identify human gut microbes that undergo significant and consistent changes(i.e.,in relative abundances)after transplantation into GF mice in multiple experimental settings.We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota pro-files from 1713 human-mouse pairs.Strikingly,on average,we found that only 47％of the human gut microbes could be re-established in mice at the species level,among which more than 1/3 under-went significant changes(referred to as"variable taxa").Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimen-tal settings.Consequently,about 1/3 of human samples changed their enterotypes,i.e.,significant changes in their leading species after FMT.Mice fed with a controlled diet showed a lower enter-otype change rate(23.5％)than those fed with a noncontrolled diet(49.0％),suggesting a possible solution for rescue.Most of the variable taxa have been reported to be implicated in human dis-eases,with some recognized as the causative species.Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes,provide useful informa-tion for researchers using mice in gut microbiota studies,and call for additional validations after FMT.An online database named FMT-DB is publicly available at .

Yanze Li;Wenming Cao;Na L Gao;Xing-Ming Zhao;Wei-Hua Chen

MOE Key Laboratory of Molecular Biophysics,Hubei Key Laboratory of Bioinformatics and Molecular-imaging,Department of Bioinforrnatics and Systems Biology,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China;Institute of Science and Technology for Brain-Inspired Intelligence(ISTBI),Fudan University,Shanghai 200433,China;College of Life Science,Henan Normal University,Xinxiang 453007,China

基因组蛋白质组与生物信息学报（英文版）

[1]Yanze Li;Wenming Cao;Na L Gao;Xing-Ming Zhao;Wei-Hua Chen-.Consistent Alterations of Human Fecal Microbes After Transplantation into Germ-free Mice)[J].基因组蛋白质组与生物信息学报（英文版）,2022(02):382-393

enterotypes,otype,noncontrolled

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