TY - JOUR T1 - Defined microbiota transplant restores Th17/RORγt<sup>+</sup> regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas JF - bioRxiv DO - 10.1101/844662 SP - 844662 AU - Graham J. Britton AU - Eduardo J. Contijoch AU - Matthew P. Spindler AU - Varun Aggarwala AU - Gerold Bongers AU - Lani San Mateo AU - Andrew Baltus AU - Anuk Das AU - Dirk Gevers AU - Thomas J. Borody AU - Nadeem O. Kaakoush AU - Michael A. Kamm AU - Hazel Mitchell AU - Sudarshan Paramsothy AU - Jose C. Clemente AU - Jean-Frederic Colombel AU - Marla C. Dubinsky AU - Ari Grinspan AU - Jeremiah J. Faith Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/16/844662.abstract N2 - The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases, where clinical trials of fecal microbiota transplant have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells and a deficit in the tolerogenic RORγt+ Treg cell subset. Transplanting healthy donor-derived microbiota into mice colonized with human IBD microbiotas lead to induction of RORγt+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn’s disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, correlated with a reduction in Th17 cells. ER -