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Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape. Proc Natl Acad Sci U S A 2023 Jun 06;120(23):e2216908120



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Pubmed Central ID




Scopus ID

2-s2.0-85160593821 (requires institutional sign-in at Scopus site)   1 Citation


Succinate produced by the commensal protist Tritrichomonas musculis (T. mu) stimulates chemosensory tuft cells, resulting in intestinal type 2 immunity. Tuft cells express the succinate receptor SUCNR1, yet this receptor does not mediate antihelminth immunity nor alter protist colonization. Here, we report that microbial-derived succinate increases Paneth cell numbers and profoundly alters the antimicrobial peptide (AMP) landscape in the small intestine. Succinate was sufficient to drive this epithelial remodeling, but not in mice lacking tuft cell chemosensory components required to detect this metabolite. Tuft cells respond to succinate by stimulating type 2 immunity, leading to interleukin-13-mediated epithelial and AMP expression changes. Moreover, type 2 immunity decreases the total number of mucosa-associated bacteria and alters the small intestinal microbiota composition. Finally, tuft cells can detect short-term bacterial dysbiosis that leads to a spike in luminal succinate levels and modulate AMP production in response. These findings demonstrate that a single metabolite produced by commensals can markedly shift the intestinal AMP profile and suggest that tuft cells utilize SUCNR1 and succinate sensing to modulate bacterial homeostasis.

Author List

Fung C, Fraser LM, BarrĂ³n GM, Gologorsky MB, Atkinson SN, Gerrick ER, Hayward M, Ziegelbauer J, Li JA, Nico KF, Tyner MDW, DeSchepper LB, Pan A, Salzman NH, Howitt MR


Amy Y. Pan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anti-Infective Agents
Intestinal Mucosa
Intestine, Small
Succinic Acid