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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,6,6]]},"abstract":"<jats:p>\n                    Succinate produced by the commensal protist\n                    <jats:italic>Tritrichomonas musculis<\/jats:italic>\n                    (\n                    <jats:italic>T. mu<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2216908120","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T13:31:38Z","timestamp":1685453498000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1693-5719","authenticated-orcid":false,"given":"Connie","family":"Fung","sequence":"first","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA 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Toma , Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. J. Clin. Invest. 118, 2526\u20132534 (2008).","journal-title":"J. Clin. 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R. Gerrick Metabolic diversity in commensal protists regulates intestinal immunity and trans-kingdom competition. bioRxiv [Preprint]. https:\/\/doi.org\/10.1101\/2022.08.26.505490 (Accessed 27 August 2022).","DOI":"10.1101\/2022.08.26.505490"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.1900099"},{"key":"e_1_3_4_66_2","unstructured":"C. Fung L. M. Fraser Fung_Fraser_Tuft_Paneth. Stanford Digital Repository. https:\/\/purl.stanford.edu\/pr220nz2789. Deposited 2 August 2022."},{"key":"e_1_3_4_67_2","unstructured":"C. Fung L. M. Fraser tmu-smallintestine-visium. Howitt Lab Github. https:\/\/github.com\/Howittlab\/tmu-smallintestine-visium. Deposited 15 May 2023."},{"key":"e_1_3_4_68_2","unstructured":"C. Fung L. M. Fraser SubmissionID: SUB11971783 BioProject ID: PRJNA873680. NCBI sra. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA873680. Deposited 22 August 2022."},{"key":"e_1_3_4_69_2","unstructured":"C. Fung L. M. 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