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 profiles 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 underwent 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 experimental 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 enterotype 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 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. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.

将人类粪便样本的粪便微生物群移植(FMT) 移植到无菌 (GF) 小鼠中可用于建立肠道微生物群与人类表型之间的因果关系。然而，由于人和小鼠肠道之间的内在差异以及两种生物的不同饮食，可能无法通过 FMT 在小鼠中复制人类表型；同样，在小鼠模型中有效的治疗方法可能对人类无效。在这项研究中，我们旨在鉴定在多个实验环境中移植到 GF 小鼠后经历显着和一致变化（即相对丰度）的人类肠道微生物。我们收集了16S rDNA-seq 来自四项已发表研究的数据，并分析了 1713 对人鼠的肠道微生物群概况。令人惊讶的是，平均而言，我们发现只有 47% 的人类肠道微生物可以在物种水平上在小鼠体内重建，其中超过 1/3 发生了显着变化（称为“可变类群”）。大多数经历过显着变化的人类肠道微生物在多个人鼠对和实验环境中是一致的。因此，大约 1/3 的人类样本改变了它们的肠型，即, FMT 后其主导物种发生显着变化。用受控饮食喂养的小鼠肠型变化率 (23.5%) 低于用非受控饮食喂养的小鼠 (49.0%)，这表明一种可能的救援解决方案。据报道，大多数可变类群与人类疾病有关，其中一些被认为是致病物种。我们的结果强调了使用小鼠模型复制人类肠道微生物群相关表型的挑战，为在肠道微生物群研究中使用小鼠的研究人员提供了有用的信息，并呼吁在 FMT 后进行额外的验证。名为 FMT-DB 的在线数据库可在 http://fmt2mice.humangut.info/#/ 上公开获得。