We thank all members of the Mucida laboratory, past and present, for assistance, discussions and reading of the manuscript; B. Reis for figure preparation; F. Matheis for propagating S. venezuelensis; A. Rogoz and S. Gonzalez for the maintenance of mice; T. Rendon and B. Lopez for genotyping; K. Gordon and K. Chosphel for assistance with cell sorting; the Rockefeller University Bio-imaging Research Center for assistance with microscopy and image analysis; the Rockefeller University Genomics Center for RNA sequencing; Rockefeller University employees for assistance; M. Nussenzweig, G. Victora and J. Lafaille and their respective laboratory members for discussions and suggestions; D. Littman and M. Xu (NYU) for 7B8tg mice and faeces from SFB monocolonized mice; and S. Galli and K. Matsushita (Stanford University) for providing S. venezuelensis and guidance on how to maintain it. This work was supported by a Swiss National Science Foundation postdoctoral fellowship and University of Chicago start-up funds (D.E.); a CAPES fellowship (M.C.C.C.); an NIH F31 Kirchstein Fellowship, Philip M. Levine Fellowship, and Kavli Neural Systems Institute Graduate Fellowship (P.A.M.); the Leona M. and Harry B. Helmsley Charitable Trust, the Crohn’s & Colitis Foundation of America Senior Research Award, the Burroughs Wellcome Fund PATH Award, and National Institute of Health grants R21AI31188, R01DK113375 and R01DK093674 (D.M.).

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Nature thanks Rodney Newberry and the other anonymous reviewer(s) for their contribution to the peer review of this work.