{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:02:56Z","timestamp":1794045776209,"version":"4.8.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cathay General Hospital, Taiwan","award":["CGH-MR-A10709"],"award-info":[{"award-number":["CGH-MR-A10709"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Periodontal disease (PD) is one of the most prevalent disorders globally and is strongly associated with many other diseases. Inflammatory bowel disease (IBD), an inflammatory condition of the colon and the small intestine, is reported to be associated with PD through undetermined mechanisms. We analyzed taxonomic assignment files from the Crohn\u2019s Disease Viral and Microbial Metagenome Project (PRJEB3206). The abundance of Porphyromonadaceae in fecal samples was significantly different between patients with Crohn\u2019s disease and control volunteers. Dextran sulfate sodium was used to induce colitis in mice to reveal the effect of this periodontopathic pathogen in vivo. After intrarectal implantation of Porphyromonas gingivalis (Pg)\u2014the primary pathogen causing PD\u2014the disease activity index score, colonic epithelial loss, and inflammatory cell infiltration were intensified. In addition, tumor necrosis factor-\u03b1 and interleukin-6 showed the highest levels in Pg-infected colons. This revealed the importance of Pg in the exacerbation of IBD. Thus, simultaneous treatment of PD should be considered for people with IBD. Moreover, implantation of Pg in the rectum worsened the clinical symptoms of colitis in mice. Because Pg participates in the pathogenesis of IBD, reducing the chances of it entering the intestine might prevent the worsening of this disorder.<\/jats:p>","DOI":"10.3390\/pathogens11010084","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T20:33:04Z","timestamp":1641933184000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Periodontopathic Pathogen, Porphyromonas gingivalis, Involves a Gut Inflammatory Response and Exacerbates Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Yu-Chen","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Dentistry, Cathay General Hospital, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan"},{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Long","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cathay General Hospital, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo-Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Graduate School of Health Industry Management, Ching Kuo Institute of Management and Health, Keelung City 20301, Taiwan"},{"name":"Department of Oral Hygiene Care, Ching Kuo Institute of Management and Health, Keelung City 20301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Jung","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-0521","authenticated-orcid":false,"given":"Ting-Lin","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Oral Hygiene Care, Ching Kuo Institute of Management and Health, Keelung City 20301, Taiwan"},{"name":"Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","unstructured":"Gasner, N.S., and Schure, R.S. (2021, October 15). Periodontal Disease, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554590\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","article-title":"Periodontal diseases","volume":"366","author":"Pihlstrom","year":"2005","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/epirev\/mxx006","article-title":"Periodontal Disease, Tooth Loss, and Cancer Risk","volume":"39","author":"Michaud","year":"2017","journal-title":"Epidemiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/prd.12227","article-title":"Periodontal complications with age","volume":"78","author":"Persson","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_5","doi-asserted-by":"crossref","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":"Periodontology 2000"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/prd.12329","article-title":"Periodontal disease and cancer: Epidemiologic studies and possible mechanisms","volume":"83","author":"Nwizu","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"465","DOI":"10.4081\/oncol.2020.465","article-title":"Periodontitis and oral cancer - current concepts of the etiopathogenesis","volume":"14","author":"Irani","year":"2020","journal-title":"Oncol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jdent.2009.10.007","article-title":"The association between periodontal disease and cancer: A review of the literature","volume":"38","author":"Fitzpatrick","year":"2010","journal-title":"J. Dent."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12903-020-01156-w","article-title":"Association between periodontitis and all-cause and cancer mortality: Retrospective elderly community cohort study","volume":"20","author":"Chung","year":"2020","journal-title":"BMC Oral Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103221","DOI":"10.1016\/j.critrevonc.2021.103221","article-title":"Association of periodontitis and tooth loss with liver cancer: A systematic review","volume":"159","author":"Ibraheem","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/prd.12296","article-title":"The role of the microbiota in periodontal disease","volume":"83","author":"Curtis","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/1029857","article-title":"Chronic Inflammation as a Link between Periodontitis and Carcinogenesis","volume":"2019","author":"Hoare","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1055\/s-0037-1602237","article-title":"Colorectal Cancer in Inflammatory Bowel Disease","volume":"31","author":"Stidham","year":"2018","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cgh.2019.07.005","article-title":"Ulcerative Colitis and Crohn\u2019s Disease Have Similar Burden and Goals for Treatment","volume":"18","author":"Ananthakrishnan","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"684486","DOI":"10.3389\/fphar.2021.684486","article-title":"Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease","volume":"12","author":"Duan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12903-020-1053-5","article-title":"Periodontitis and inflammatory bowel disease: A meta-analysis","volume":"20","author":"She","year":"2020","journal-title":"BMC Oral Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/idj.12542","article-title":"Increased risks of dental caries and periodontal disease in Chinese patients with inflammatory bowel disease","volume":"70","author":"Zhang","year":"2020","journal-title":"Int. Dent. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1080\/00016357.2020.1859132","article-title":"Association between periodontal disease and inflammatory bowel disease: A systematic review and meta-analysis","volume":"79","author":"Vega","year":"2021","journal-title":"Acta Odontol. Scand."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lin, C.-Y., Tseng, K.-S., Liu, J.-M., Chuang, H.-C., Lien, C.-H., Chen, Y.-C., Lai, C.-Y., Yu, C.-P., and Hsu, R.-J. (2018). Increased Risk of Ulcerative Colitis in Patients with Periodontal Disease: A Nationwide Population-Based Cohort Study. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15112602"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/jre.12733","article-title":"Inflammasomes and their regulation in periodontal disease: A review","volume":"55","author":"Aral","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_21","doi-asserted-by":"crossref","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":"ref_22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nri3430","article-title":"Role of the gut microbiota in immunity and inflammatory disease","volume":"13","author":"Kamada","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1136\/gutjnl-2012-303955","article-title":"Recent advances in inflammatory bowel disease: Mucosal immune cells in intestinal inflammation","volume":"62","author":"Cader","year":"2013","journal-title":"Gut"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1159\/000338120","article-title":"Commensal-Innate Immune Miscommunication in IBD Pathogenesis","volume":"30","author":"Cario","year":"2012","journal-title":"Dig. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1600-0757.2009.00333.x","article-title":"Contribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis","volume":"54","author":"Jain","year":"2010","journal-title":"Periodontology 2000"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1177\/154405910608500502","article-title":"Porphyromonas gingivalis-Epithelial Cell Interactions in Periodontitis","volume":"85","author":"Andrian","year":"2006","journal-title":"J. Dent. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"259074","DOI":"10.1155\/2015\/259074","article-title":"Relationship between Periodontitis and Rheumatoid Arthritis: Review of the Literature","volume":"2015","author":"Melo","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fiorillo, L., Cervino, G., Laino, L., D\u2019Amico, C., Mauceri, R., Tozum, T.F., Gaeta, M., and Cicci\u00f9, M. (2019). Porphyromonas gingivalis, Periodontal and Systemic Implications: A Systematic Review. Dent. J., 7.","DOI":"10.3390\/dj7040114"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1007\/s00535-012-0738-1","article-title":"Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice","volume":"48","author":"Furusho","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1563405","DOI":"10.1080\/20002297.2018.1563405","article-title":"Assessing the role of Porphyromonas gingivalis in periodontitis to determine a causative relationship with Alzheimer\u2019s disease","volume":"11","author":"Singhrao","year":"2019","journal-title":"J. Oral Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fimmu.2012.00107","article-title":"Chronic intestinal inflammation: Inflammatory bowel disease and colitis-associated colon cancer","volume":"3","author":"Rubin","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15.25.1","DOI":"10.1002\/0471142735.im1525s104","article-title":"Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_34","first-page":"4557","article-title":"A guide to histomorphological evaluation of intestinal inflammation in mouse models","volume":"7","author":"Erben","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/ibd.20148","article-title":"Il-6 signaling in inflammatory bowel disease: Pathophysiological role and clinical relevance","volume":"13","author":"Mudter","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/19490976.2015.1121364","article-title":"The Intersection of TNF, IBD and the Microbiome","volume":"7","author":"Nakatsu","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41419-018-1275-5","article-title":"Elevated apoptosis impairs epithelial cell turnover and shortens villi in TNF-driven intestinal inflammation","volume":"10","author":"Parker","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1136\/gutjnl-2017-314562","article-title":"Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn\u2019s disease (ANDANTE I and II)","volume":"68","author":"Danese","year":"2019","journal-title":"Gut"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/qjmed\/hcu078","article-title":"Periodontal disease with treatment reduces subsequent cancer risks","volume":"107","author":"Hwang","year":"2014","journal-title":"QJM Int. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3233\/ADR-170017","article-title":"Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer\u2019s Disease","volume":"1","author":"Carter","year":"2017","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8128","DOI":"10.1038\/s41598-019-44512-9","article-title":"Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal bone loss","volume":"9","author":"Ebbers","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3748\/wjg.v22.i3.1078","article-title":"Role of antibiotics for treatment of inflammatory bowel disease","volume":"22","author":"Nitzan","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/apt.13454","article-title":"Adjuvant use of antibiotics with corticosteroids in inflammatory bowel disease exacerbations requiring hospitalisation: A retrospective cohort study and meta-analysis","volume":"43","author":"Gupta","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/apt.14384","article-title":"Review article: The gut microbiome in inflammatory bowel disease-avenues for microbial management","volume":"47","author":"McIlroy","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4103\/1735-3327.104866","article-title":"Systemic antibiotic therapy in periodontics","volume":"9","author":"Kapoor","year":"2012","journal-title":"Dent. Res. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s42826-019-0029-6","article-title":"Implication of Porphyromonas gingivalis in colitis and homeostasis of intestinal epithelium","volume":"35","author":"Seo","year":"2019","journal-title":"Lab. Anim. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/jcpe.13396","article-title":"The prevalence and severity of periodontal disease in Mainland China: Data from the Fourth National Oral Health Survey (2015\u20132016)","volume":"48","author":"Jiao","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2146460","DOI":"10.1155\/2020\/2146160","article-title":"Global Prevalence of Periodontal Disease and Lack of Its Surveillance","volume":"2020","author":"Nazir","year":"2020","journal-title":"Sci. World J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.addr.2007.07.003","article-title":"Mouse models of inflammatory bowel disease","volume":"59","author":"Wirtz","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_50","first-page":"1341","article-title":"Animal models of ulcerative colitis and their application in drug research","volume":"7","author":"Low","year":"2013","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"137","DOI":"10.12938\/bmfh.2016-007","article-title":"Protective effects of heat-killed Lactococcus lactis subsp. lactis BF3, isolated from the intestine of chum salmon, in a murine model of DSS-induced inflammatory bowel disease","volume":"35","author":"Nakata","year":"2016","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6742652","DOI":"10.1155\/2017\/6742652","article-title":"Comparative Evaluation between Sulfasalazine Alone and in Combination with Herbal Medicine on DSS-Induced Ulcerative Colitis Mice","volume":"2017","author":"Shin","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1038\/ctg.2013.9","article-title":"Study of the Viral and Microbial Communities Associated With Crohn\u2019s Disease: A Metagenomic Approach","volume":"4","author":"Nos","year":"2013","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/labinvest.2008.28","article-title":"Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: Mucin 2-interleukin 10-deficient mice","volume":"88","author":"Bouma","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"239617","DOI":"10.1155\/2012\/239617","article-title":"Suppression of Dextran Sulfate Sodium-Induced Colitis in Mice by Radon Inhalation","volume":"2012","author":"Nishiyama","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3892\/ol.2014.2781","article-title":"Immunohistochemical staining of tumor necrosis factor-\u03b1 and interleukin-10 in benign and malignant ovarian neoplasms","volume":"9","author":"Jammal","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Thongchot, S., Vidoni, C., Ferraresi, A., Loilome, W., Khuntikeo, N., Sangkhamanon, S., Titapun, A., Isidoro, C., and Namwat, N. (2021). Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse. 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