Consistent Alterations Of Human Fecal Microbes After Transplantation Into Germ-free Mice

Fecal microbiota transplant(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 underwent significant and consistent changes(i.e.,in relative abundances)after transplantation into GF mice in multiple experimental settings.We collected 16 S r RNA sequencing data from four previous published studies and analyzed the gut microbiota profiles from 1,713 human-mouse pairs;strikingly,on average,we found that <50% of the human gut microbes could be re-established in mice at the species level,among which,more than 1/3 underwent significant changes(referred to as “variable microbes”).Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimental settings.Consequently,one-third of human samples had different enterotypes,i.e.,significant changes in their leading species after FMT.Mice fed a controlled diet showed a significant decrease in the enterotype change rate(?25%)compared with those fed a noncontrolled diet(?50%),suggesting a possible solution for rescue.Strikingly,most of the variable microbes have been implicated in human diseases,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 information for researchers using mice in gut microbiota studies and call for additional validations after FMT.To make our study more useful to researchers,we created an online database to include all the data and our results and intended to keep it updated in the future.The database is publicly available at: http://fmt2 mice.humangut.info/#/.