A single fecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis. Rat gut metagenome, mouse gut metagenome

BackgroundFecal microbiota transplantation (FMT) is a novel therapy for inflammatory bowel diseases. Even though remission occurs at very low rates in clinical trials, little investigation using animal models has been done to understand this strategy. Here we evaluated the performance of the mouse and rat as a model for human microbiota engraftment. We then characterized the effect of a single human stool transfer (HST) on a humanized rodent model of DSS-induced colitis by examining colonic and fecal microbial communities and clinical manifestations in a longitudinal setting.ResultsOur findings indicated that the microbiome of rats shows greater similarity to that of humans, in terms of composition and structure, while the microbiome of mice shows less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated fecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These alterations in fecal and colonic microbe communities led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by retrieving DSS combined with HST caused a faster and greater recovery at both the microbiome and clinical manifestation level.ConclusionsOur results not only indicate that rat represents a better model than mouse for the engraftment of human microbiota, but also show that the efficacy of HST could be enhanced when inflammation induction was withdrawn. Finally, our data promote new strategies based on the combination of anti-inflammatory drugs with fecal transplantation.