Journal article

Defined microbiota transplant restores Th17/ROR gamma t( ) regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas

Graham J Britton, Eduardo J Contijoch, Matthew P Spindler, Varun Aggarwala, Belgin Dogan, Gerold Bongers, Lani San Mateo, Andrew Baltus, Anuk Das, Dirk Gevers, Thomas J Borody, Nadeem O Kaakoush, Michael A Kamm, Hazel Mitchell, Sudarshan Paramsothy, Jose C Clemente, Jean-Frederic Colombel, Kenneth W Simpson, Marla C Dubinsky, Ari Grinspan Show all

Proceedings of the National Academy of Sciences of USA | NATL ACAD SCIENCES | Published : 2020

Abstract

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 (IBDs), where clinical trials of fecal microbiota transplantation 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..

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Grants

Awarded by NIH National Institute of General Medical Sciences Grant


Awarded by National Institute of Diabetes and Digestive Diseases


Awarded by CCFA Microbiome Innovation Award


Awarded by NIH


Awarded by Cancer Center Support Grant


Funding Acknowledgements

We thank C. Fermin, E. Vazquez, and G. N. Escano (Mount Sinai Immunology Institute Gnotobiotic Facility) and E. Ariztia, O. Vennaro, I. Mogno, and Z. Li for technical support. This work was supported in part by the staff and resources of Scientific Computing and of the Flow Cytometry Core at the Icahn School of Medicine at Mount Sinai. G.J.B. is supported by a Research Fellowship Award from the Crohn's and Colitis Foundation of America (CCFA). This work was further supported by NIH National Institute of General Medical Sciences Grant GM108505 and National Institute of Diabetes and Digestive Diseases Grants DK112978 and DK124133; the Janssen Human Microbiome Institute; a CCFA Microbiome Innovation Award (362048); the New York Crohn's Foundation (J.J.F.); NIH Grants DK112679 (to E.J.C.) and AI078892 (to M.P.S.); and a CCFA Research Fellowship Award (to V.A.). Next-generation sequencing was performed at the New York University School of Medicine by the Genome Technology Center that is partially supported by Cancer Center Support Grant P30CA016087.