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Several cohort studies have shown that cigarette smoking (CS) is a risk factor for CD, but it has protective potential for UC. Although CS has been shown to cause different effects on UC and CD, the underlying mechanisms have not been fully determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Colitis was induced in CS-exposed mice using two different chemical-induced models: dextran sodium\u00a0sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS). We examined pathology of the colon, effector lymphocytes, composition of the microbiota, and intestinal metabolites. We also examined the effect of an intestinal metabolite, 4-hydroxybenzoic acid (4-HBA), on DSS- and TNBS-induced colitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CS exposure attenuated the pathogenesis of DSS-induced colitis by an increase in regulatory T cells (Tregs) accompanied by an increase in short-chain fatty acid production. By contrast, CS exacerbated TNBS-induced colitis by an increase in effector T cells and the abundance of\n                      <jats:italic>Enterobacteriaceae<\/jats:italic>\n                      , which were correlated with the pathogenesis of IBD. The administration of 4-HBA, which was remarkably increased by CS exposure in the DSS-induced colitis model, suppressed the colonic inflammation accompanying the induction of Tregs and suppression of effector T cells, but exerted no apparent protective effect against TNBS-induced colitis model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CS may regulate colonic inflammation by altering the composition of the microbiota, intestinal metabolites, and immune responses. Additionally, mechanistic findings identified 4-HBA as a potential therapeutic target and provided insights into the development of new therapeutic approaches for UC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00535-026-02484-4","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:24:52Z","timestamp":1785515092000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolite 4-hydroxybenzoic acid, modulated by cigarette smoke exposure, functions as a protective factor in dextran sodium sulfate-induced colitis"],"prefix":"10.1007","author":[{"given":"Masahiro","family":"Kitabatake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Nishioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaito","family":"Yasuike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Ouji-Sageshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1728-2449","authenticated-orcid":false,"given":"Toshihiro","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2484_CR1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nature10208","volume":"474","author":"KJ Maloy","year":"2011","unstructured":"Maloy KJ, Powrie F. 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