{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:54:57Z","timestamp":1791924897768,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether periodontitis promotes intestinal inflammation through gut microbiota\u2013mediated suppression of the GPR109A receptor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Periodontitis was induced by ligatures in C57BL\/6J mice under normal chow or high-fructose diet. Periodontal destruction was evaluated by micro-computed tomography and hematoxylin and eosin staining. Colonic GPR109A expression, intestinal epithelial integrity, as well as intestinal and systemic inflammation were assessed by histology and immunostaining, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Short-chain fatty acids (SCFAs) in colonic contents were quantified by GC\u2013MS\/MS. Further, the probiotic strain CBM588 was supplemented to two groups of mice (CP\/LP group) to alleviate periodontitis-induced inflammation, and GPR109A expression was detected. To investigate the role of periodontitis-associated gut microbiota, fecal microbiota from control (GF-CON) and ligatured (GF-LIG) mice were transplanted into germ-free recipients, and colonic GPR109A levels and inflammatory responses were analyzed. Finally, GPR109A function was modulated by administration of GSK256073 and mepenzolate bromide in ligatured mice, and corresponding changes in tight junctional integrity as well as intestinal and systemic inflammation were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Periodontitis significantly downregulated the expression of colonic GPR109A and disrupted the localization of ZO-1 and Occludin. Probiotic supplementation restored GPR109A expression and rescued ZO-1 distribution. Fecal microbiota transplantation from periodontitis donors led to GPR109A suppression, tight junction impairment, and inflammatory upregulation in germ-free mice, confirming a microbiota-dependent mechanism. Activation of GPR109A reversed barrier disruption and reduced pro-inflammatory cytokine levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Periodontitis promotes colonic inflammation by gut microbiota-induced suppression of GPR109A receptor, leading to the destruction of the epithelial barrier. Activation of GPR109A restores barrier function and attenuates inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1761932","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T06:47:09Z","timestamp":1771915629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Periodontitis promotes intestinal inflammation through gut microbiota\u2013mediated suppression of GPR109A"],"prefix":"10.3389","volume":"16","author":[{"given":"Xinyue","family":"Wang","sequence":"first","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghan","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Yao","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jia","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Du","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangzheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhua","family":"Yan","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","volume-title":"AVMA guidelines for the euthanasia of animals: 2020 edition","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/nu17152538","article-title":"The oral-gut microbiota axis across the lifespan: new insights on a forgotten interaction","volume":"17","author":"Azzolino","year":"2025","journal-title":"Nutrients"},{"key":"B3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41368-022-00183-3","article-title":"Periodontitis may induce gut microbiota dysbiosis via salivary microbiota","volume":"14","author":"Bao","year":"2022","journal-title":"Int. J. Oral. Sci."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/medicina56060272","article-title":"Periodontitis, low-grade inflammation and systemic health: a scoping review","volume":"56","author":"Cecoro","year":"2020","journal-title":"Med. (Kaunas)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"102539","DOI":"10.1016\/j.cbpa.2024.102539","article-title":"Microbial metabolite-receptor interactions in the gut microbiome","volume":"83","author":"Chang","year":"2024","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02079","article-title":"G protein-coupled receptor 109A and host microbiota modulate intestinal epithelial integrity during sepsis","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2573045","DOI":"10.1080\/19490976.2025.2573045","article-title":"Microbiota shape the colon epithelium controlling inter-crypt absorptive goblet cells via butyrate-GP R109A signalling","volume":"17","author":"Dias Nirello","year":"2025","journal-title":"Gut Microbes"},{"key":"B8","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/s41385-022-00538-3","article-title":"Critical roles of G protein-coupled receptors in regulating intestinal homeostasis and inflammatory bowel disease","volume":"15","author":"Feng","year":"2022","journal-title":"Mucosal Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s13098-025-01845-y","article-title":"Global burden of high sugar-sweetened beverage consumption among young adults","volume":"17","author":"Ge","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"107780","DOI":"10.1016\/j.phrs.2025.107780","article-title":"Reinforcing gut integrity: A systematic review and meta-analysis of clinical trials assessing probiotics, synbiotics, and prebiotics on intestinal permeability markers","volume":"216","author":"Ghorbani","year":"2025","journal-title":"Pharmacol. Res."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583652","article-title":"G protein-coupled receptor 109A maintains the intestinal integrity and protects against ETEC mucosal infection by promoting IgA secretion","volume":"11","author":"Gong","year":"2020","journal-title":"Front. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/s41577-020-00488-6","article-title":"Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities","volume":"21","author":"Hajishengallis","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/prd.12337","article-title":"A public health approach for prevention of periodontal disease","volume":"84","author":"Janakiram","year":"2020","journal-title":"Periodontol 2000"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010041","article-title":"Colon-targeted trans-cinnamic acid Ameliorates rat colitis by activating GPR109A","volume":"15","author":"Kang","year":"2022","journal-title":"Pharmaceutics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.12771\/emj.2025.00101","article-title":"Relationship between periodontitis and systemic health conditions: a narrative review","volume":"48","author":"Kim","year":"2025","journal-title":"Ewha Med. J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/s41591-024-03345-4","article-title":"Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries","volume":"31","author":"Lara-Castor","year":"2025","journal-title":"Nat. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1177\/00220345211009449","article-title":"Gut microbiota may mediate the influence of periodontitis on prediabetes","volume":"100","author":"Li","year":"2021","journal-title":"J. Dent. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1111\/jcpe.13708","article-title":"Periodontitis may impair the homeostasis of systemic bone through regulation of gut microbiota in ApoE(-\/-) mice","volume":"49","author":"Li","year":"2022","journal-title":"J. Clin. Periodontol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158332","article-title":"Niacin improves intestinal health through up-regulation of AQPs expression induced by GPR109A","volume":"23","author":"Liu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"6734","DOI":"10.1038\/ncomms7734","article-title":"Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome","volume":"6","author":"Macia","year":"2015","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1098386","article-title":"Role of gut microbiota in infectious and inflammatory diseases","volume":"14","author":"Maciel-Fiuza","year":"2023","journal-title":"Front. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1093\/ibd\/izac090","article-title":"The impact of periodontitis on inflammatory bowel disease activity","volume":"29","author":"Madsen","year":"2023","journal-title":"Inflammation Bowel Dis."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.54584","article-title":"Periodontitis and inflammatory bowel disease: A review","volume":"16","author":"Ozayzan","year":"2024","journal-title":"Cureus"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000003326","article-title":"Periodontitis and the incidence of inflammatory bowel diseases: A nationwide Population-Based cohort study","volume":"120","author":"Park","year":"2025","journal-title":"Am. J. Gastroenterol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1186\/s12916-023-03139-4","article-title":"Periodontitis and systemic inflammation as independent and interacting risk factors for mortality: evidence from a prospective cohort study","volume":"21","author":"Pink","year":"2023","journal-title":"BMC Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41522-023-00462-9","article-title":"Periodontitis salivary microbiota exacerbates colitis-induced anxiety-like behavior via gut microbiota","volume":"9","author":"Qian","year":"2023","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B27","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1177\/00220345211049781","article-title":"Periodontitis salivary microbiota worsens colitis","volume":"101","author":"Qian","year":"2022","journal-title":"J. Dent. Res."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1440216","article-title":"Obesity and periodontitis: a comprehensive review of their interconnected pathophysiology and clinical implications","volume":"11","author":"Reytor-Gonz\u00e1lez","year":"2024","journal-title":"Front. Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41598-021-03787-7","article-title":"GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity","volume":"12","author":"Rubbino","year":"2022","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/jcpe.13881","article-title":"Periodontitis and the incidence of metabolic syndrome: An 8-year longitudinal study of an adult Japanese cohort","volume":"51","author":"Saito","year":"2024","journal-title":"J. Clin. Periodontol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051348","article-title":"High intake of sugar and the balance between pro-and anti-inflammatory gut bacteria","volume":"12","author":"Satokari","year":"2020","journal-title":"Nutrients"},{"key":"B32","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.immuni.2013.12.007","article-title":"Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis","volume":"40","author":"Singh","year":"2014","journal-title":"Immunity"},{"key":"B33","doi-asserted-by":"publisher","first-page":"F835","DOI":"10.1152\/ajprenal.00505.2019","article-title":"Exploring the role of the metabolite-sensing receptor GPR109a in diabetic nephropathy","volume":"318","author":"Snelson","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/nu11112817","article-title":"Butyric acid and leucine induce \u03b1-defensin secretion from small intestinal Paneth cells","volume":"11","author":"Takakuwa","year":"2019","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1158\/0008-5472.CAN-08-4466","article-title":"GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon","volume":"69","author":"Thangaraju","year":"2009","journal-title":"Cancer Res."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1430001","article-title":"The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Immunol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1478362","article-title":"Periodontal bacteria influence systemic diseases through the gut microbiota","volume":"14","author":"Xi","year":"2024","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"101718","DOI":"10.1016\/j.xcrm.2024.101718","article-title":"Dietary vitamin B3 supplementation induces the antitumor immunity against liver cancer via biased GPR109A signaling in myeloid cell","volume":"5","author":"Yang","year":"2024","journal-title":"Cell Rep. Med."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.15058","article-title":"Clostridium butyricum MIYAIRI 588 alleviates periodontal bone loss in mice with diabetes mellitus","volume":"1529","author":"Zhang","year":"2023","journal-title":"Ann N Y Acad Sci."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1478374","article-title":"Advances in research on the role of high carbohydrate diet in the process of inflammatory bowel disease (IBD)","volume":"15","author":"Zhang","year":"2024","journal-title":"Front. Immunol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1143548","article-title":"Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials","volume":"14","author":"Zheng","year":"2023","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1761932\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T06:47:10Z","timestamp":1771915630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1761932\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":41,"alternative-id":["10.3389\/fcimb.2026.1761932"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1761932","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"article-number":"1761932"}}