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Previous studies showed that sensing of symbiotic bacteria by nucleotide\u2010binding oligomerization domain\u2010containing protein 2 (Nod2) regulates antibody responses in response to nasal immunization with antigen and cholera toxin (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>). In this study, we examined the role of the microbiota in the adjuvant activity of <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> induced after oral immunization with antigen. Germ\u2010free (GF) mice showed impaired production of antibody responses and T\u2010cell\u2010specific cytokines after oral immunization when compared with that observed in conventionally raised mice. Similar to GF mice, Nod2\u2010deficient mice showed reduced humoral responses upon oral immunization with antigen and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>. Treatment with <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> enhanced the production of interleukin\u20101<jats:italic>\u03b2<\/jats:italic> (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>), but not tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> or <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201012p40, induced by stimulation of dendritic cells with muramyl dipeptide, the Nod2 ligand. Mechanistically, the enhanced production of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> induced by muramyl dipeptide and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> stimulation required Nod2 and was mediated by both increased synthesis of pro\u2010<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> and caspase\u20101 activation. Furthermore, antigen\u2010specific antibody and cytokine responses induced by <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> were impaired in orally immunized <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>\u2010deficient mice. Collectively, our results indicate that Nod2 stimulation by symbiotic bacteria contributes to optimal <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010mediated antigen\u2010specific oral vaccination through the induction of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> production.<\/jats:p>","DOI":"10.1111\/imm.13105","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T06:00:24Z","timestamp":1567490424000},"page":"219-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin\u20101<i>\u03b2<\/i>"],"prefix":"10.1111","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5137-2213","authenticated-orcid":false,"given":"Donghyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"},{"name":"Comprehensive Cancer Center University of Michigan Medical School Ann Arbor MI USA"},{"name":"Department of Microbiology and Immunology Seoul National University College of Medicine Seoul South Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Integrative Rheumatoid Transcriptomics and Dynamics the Catholic University of Korea Seoul South 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