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In this study, we report that depletion of gut bacteria significantly decreased mucosal and systemic Ab responses in mice orally immunized with OVA and CT. Feeding mice short-chain fatty acids (SCFAs) promoted Ab responses elicited by CT, and, more importantly, rescued Ab responses in antibiotic-treated mice. In addition, mice deficient in GPR43, a receptor for SCFAs, showed impaired adjuvant activity of CT. Administering CT did not promote SCFA production in the intestines; thus, SCFAs facilitated but did not directly mediate the adjuvant activity of CT. SCFAs promoted B cell Ab production by promoting dendritic cell production of BAFF and ALDH1a2, which induced B cell expression of IFN regulatory factor 4, Blimp1, and XBP1, the plasma B cell differentiation-related genes. Furthermore, when infected with Citrobacter rodentium, GPR43\u2212\/\u2212 mice exhibited decreased Ab responses and were more susceptible to infection, whereas the administration of SCFAs promoted intestinal Ab responses in wild-type mice. Our study thereby demonstrated a critical role of gut microbiota and their metabolite SCFAs in promoting mucosal adjuvant activity of CT through GPR43.<\/jats:p>","DOI":"10.4049\/jimmunol.1801068","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T16:35:18Z","timestamp":1557506118000},"page":"282-292","source":"Crossref","is-referenced-by-count":60,"title":["Microbiota Metabolite Short-Chain Fatty Acids Facilitate Mucosal Adjuvant Activity of Cholera Toxin through GPR43"],"prefix":"10.1093","volume":"203","author":[{"given":"Wenjing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"},{"name":"Department of Gastroenterology, The Shanghai Tenth People\u2019s Hospital, Tongji University , Shanghai 200072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"},{"name":"Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University , Yaan, Sichuan 611130 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangsheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feidi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"},{"name":"Department of Gastroenterology, The Shanghai Tenth People\u2019s Hospital, Tongji University , Shanghai 200072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Bilotta","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"},{"name":"Department of Gastroenterology, Qilu Hospital, Shandong University , Jinan 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxia","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb , Princeton, NJ 08540"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanju","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Shanghai Tenth People\u2019s Hospital, Tongji University , Shanghai 200072 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-7395","authenticated-orcid":false,"given":"Yingzi","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX 77555"},{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2025030418133610700_r1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.immuni.2010.09.013","article-title":"Vaccination strategies to promote mucosal antibody responses","volume":"33","author":"Chen","year":"2010","journal-title":"Immunity"},{"key":"2025030418133610700_r2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.imlet.2014.01.006","article-title":"New advances in mucosal vaccination","volume":"161","author":"Ranasinghe","year":"2014","journal-title":"Immunol. 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