{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T13:18:47Z","timestamp":1794057527757,"version":"4.8.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Probiotics have been used to treat gastrointestinal disorders. However, the effect of orally intubated probiotics on oral disease remains unclear. We assessed the potential of oral administration of <jats:italic>Lactobacillus gasseri<\/jats:italic> SBT2055 (LG2055) for <jats:italic>Porphyromonas gingivalis<\/jats:italic> infection. LG2055 treatment significantly reduced alveolar bone loss, detachment and disorganization of the periodontal ligament, and bacterial colonization by subsequent <jats:italic>P<\/jats:italic>. <jats:italic>gingivalis<\/jats:italic> challenge. Furthermore, the expression and secretion of TNF-\u03b1 and IL-6 in gingival tissue was significantly decreased in LG2055-administered mice after bacterial infection. Conversely, mouse \u03b2-defensin-14 (mBD-14) mRNA and its peptide products were significantly increased in distant mucosal components as well as the intestinal tract to which LG2055 was introduced. Moreover, IL-1\u03b2 and TNF-\u03b1 production from THP-1 monocytes stimulated with <jats:italic>P<\/jats:italic>. <jats:italic>gingivalis<\/jats:italic> antigen was significantly reduced by the addition of human \u03b2-defensin-3. These results suggest that gastrically administered LG2055 can enhance immunoregulation followed by periodontitis prevention in oral mucosa via the gut immune system; i.e., the possibility of homing in innate immunity.<\/jats:p>","DOI":"10.1038\/s41598-017-00623-9","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T13:31:42Z","timestamp":1490707902000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease"],"prefix":"10.1038","volume":"7","author":[{"given":"R.","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Hosoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kurita-Ochiai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,3]]},"reference":[{"key":"623_CR1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/j.1600-051X.1998.tb02419.x","volume":"25","author":"SS Socransky","year":"1998","unstructured":"Socransky, S. S., Haffajee, A. D., Cugini, M. A., Smith, C. & Kent, R. L. Jr. Microbial complexes in subgingival plaque. J Clin Periodontol \n                           25, 134\u2013144 (1998).","journal-title":"J Clin Periodontol"},{"key":"623_CR2","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.chom.2011.10.006","volume":"10","author":"G Hajishengallis","year":"2011","unstructured":"Hajishengallis, G. et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe \n                           10, 497\u2013506 (2011).","journal-title":"Cell Host Microbe"},{"key":"623_CR3","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1177\/0022034512453589","volume":"91","author":"RP Darveau","year":"2012","unstructured":"Darveau, R. P., Hajishengallis, G. & Curtis, M. A. Porphyromonas gingivalis as a potential community activist for disease. J Dent Res \n                           91, 816\u2013820 (2012).","journal-title":"J Dent Res"},{"key":"623_CR4","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1128\/MMBR.62.4.1244-1263.1998","volume":"62","author":"RJ Lamont","year":"1998","unstructured":"Lamont, R. J. & Jenkinson, H. F. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev \n                           62, 1244\u20131263 (1998).","journal-title":"Microbiol Mol Biol Rev"},{"key":"623_CR5","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/j.1600-0757.1999.tb00162.x","volume":"20","author":"SC Holt","year":"1999","unstructured":"Holt, S. C., Kesavalu, L., Walker, S. & Genco, C. A. Virulence factors of Porphyromonas gingivalis. Periodontol 2000 \n                           20, 168\u2013238 (1999).","journal-title":"Periodontol 2000"},{"key":"623_CR6","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1034\/j.1399-302x.2000.150601.x","volume":"15","author":"RJ Lamont","year":"2000","unstructured":"Lamont, R. J. & Jenkinson, H. F. Subgingival colonization by Porphyromonas gingivalis. Oral Microbiol Immunol \n                           15, 341\u2013349 (2000).","journal-title":"Oral Microbiol Immunol"},{"key":"623_CR7","doi-asserted-by":"publisher","first-page":"409","DOI":"10.2174\/1389203033487009","volume":"4","author":"OB-S NM","year":"2003","unstructured":"NM, O. B.-S., Veith, P. D., Dashper, S. G. & Reynolds, E. C. Porphyromonas gingivalis gingipains: the molecular teeth of a microbial vampire. Curr Protein Pept Sci \n                           4, 409\u2013426 (2003).","journal-title":"Curr Protein Pept Sci"},{"key":"623_CR8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nri3785","volume":"15","author":"G Hajishengallis","year":"2015","unstructured":"Hajishengallis, G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol \n                           15, 30\u201344 (2015).","journal-title":"Nat Rev Immunol"},{"key":"623_CR9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jped.2014.08.005","volume":"91","author":"Y Vandenplas","year":"2015","unstructured":"Vandenplas, Y., Huys, G. & Daube, G. Probiotics: an update. Jornal Pediatr \n                           91, 6\u201321 (2015).","journal-title":"Jornal Pediatr"},{"key":"623_CR10","doi-asserted-by":"crossref","unstructured":"Hammes, W. P. and R. F. Vogel. The genus Lactobacillus, p. 19\u201354. In: B. J. B. Wood and W. H. Holzapfel (ed.), The lactic acid bacteria. Volume 2. The genera of lactic acid bacteria. Blackie Academic & Professional, London. (1995).","DOI":"10.1007\/978-1-4615-5817-0_3"},{"key":"623_CR11","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1111\/1574-6976.12021","volume":"37","author":"K Selle","year":"2013","unstructured":"Selle, K. & Klaenhammer, T. R. Genomic and phenotypic evidence for probiotic influences of Lactobacillus gasseri on human health. FEMS Microbiol Rev \n                           37, 915\u2013935 (2013).","journal-title":"FEMS Microbiol Rev"},{"key":"623_CR12","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1046\/j.1365-2672.2001.01251.x","volume":"90","author":"S Fujiwara","year":"2001","unstructured":"Fujiwara, S., Seto, Y., Kimura, A. & Hashiba, H. Establishment of orally-administered Lactobacillus gasseri SBT2055SR in the gastrointestinal tract of humans and its influence on intestinal microflora and metabolism. J Appl Microbiol \n                           90, 343\u2013352 (2001).","journal-title":"J Appl Microbiol"},{"key":"623_CR13","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1348-0421.2006.tb03862.x","volume":"50","author":"H Takahashi","year":"2006","unstructured":"Takahashi, H., Fujita, T., Suzuki, Y. & Benno, Y. Monitoring and survival of Lactobacillus gasseri SBT2055 in the human intestinal tract. Microbiol Immunol \n                           50, 867\u2013870 (2006).","journal-title":"Microbiol Immunol"},{"key":"623_CR14","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3168\/jds.S0022-0302(99)75229-X","volume":"82","author":"Usman","year":"1999","unstructured":"Usman & Hosono, A. Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains. J Dairy Sci \n                           82, 243\u2013248 (1999).","journal-title":"J Dairy Sci"},{"key":"623_CR15","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1017\/S0007114507839006","volume":"99","author":"M Sato","year":"2008","unstructured":"Sato, M. et al. Effects of milk fermented by Lactobacillus gasseri SBT2055 on adipocyte size in rats. Br J Nutr \n                           99, 1013\u20131017 (2008).","journal-title":"Br J Nutr"},{"issue":"Suppl 1","key":"623_CR16","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1186\/1475-2859-10-S1-S17","volume":"10","author":"JM Wells","year":"2011","unstructured":"Wells, J. M. Immunomodulatory mechanisms of lactobacilli. Microb Cell Fact \n                           10 (Suppl 1), S17 (2011).","journal-title":"Microb Cell Fact"},{"key":"623_CR17","doi-asserted-by":"publisher","first-page":"6688","DOI":"10.4049\/jimmunol.0903984","volume":"184","author":"J Rohrl","year":"2010","unstructured":"Rohrl, J., Yang, D., Oppenheim, J. J. & Hehlgans, T. Human beta-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol \n                           184, 6688\u20136694 (2010).","journal-title":"J Immunol"},{"key":"623_CR18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.2217\/fmb.09.104","volume":"5","author":"KG Kohlgraf","year":"2010","unstructured":"Kohlgraf, K. G., Pingel, L. C., Dietrich, D. E. & Brogden, K. A. Defensins as anti-inflammatory compounds and mucosal adjuvants. Future Microbiol \n                           5, 99\u2013113 (2010).","journal-title":"Future Microbiol"},{"key":"623_CR19","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/jam.12521","volume":"117","author":"TS Kemgang","year":"2014","unstructured":"Kemgang, T. S., Kapila, S., Shanmugam, V. P. & Kapila, R. Cross-talk between probiotic lactobacilli and host immune system. J Appl Microbiol \n                           117, 303\u2013319 (2014).","journal-title":"J Appl Microbiol"},{"key":"623_CR20","doi-asserted-by":"publisher","first-page":"4828","DOI":"10.1038\/srep04828","volume":"4","author":"K Arimatsu","year":"2014","unstructured":"Arimatsu, K. et al. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep \n                           4, 4828 (2014).","journal-title":"Sci Rep"},{"key":"623_CR21","doi-asserted-by":"publisher","first-page":"567","DOI":"10.3748\/wjg.v17.i5.567","volume":"17","author":"M Chamaillard","year":"2011","unstructured":"Chamaillard, M. & Dessein, R. Defensins couple dysbiosis to primary immunodeficiency in Crohn\u2019s disease. World J Gastroenterol \n                           17, 567\u2013571 (2011).","journal-title":"World J Gastroenterol"},{"key":"623_CR22","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1111\/j.1365-2249.2007.03587.x","volume":"151","author":"M Schlee","year":"2008","unstructured":"Schlee, M. et al. Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin Exp Immunol \n                           151, 528\u2013535 (2008).","journal-title":"Clin Exp Immunol"},{"key":"623_CR23","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1128\/AAC.47.10.3349-3351.2003","volume":"47","author":"G Maisetta","year":"2003","unstructured":"Maisetta, G. et al. activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother \n                           47, 3349\u20133351 (2003).","journal-title":"Antimicrob Agents Chemother"},{"key":"623_CR24","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.4049\/jimmunol.179.2.1245","volume":"179","author":"J Shi","year":"2007","unstructured":"Shi, J. et al. A novel role for defensins in intestinal homeostasis: regulation of IL-1beta secretion. J Immunol \n                           179, 1245\u20131253 (2007).","journal-title":"J Immunol"},{"key":"623_CR25","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.4049\/jimmunol.0804187","volume":"183","author":"K Miles","year":"2009","unstructured":"Miles, K. et al. Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol \n                           183, 2122\u20132132 (2009).","journal-title":"J Immunol"},{"key":"623_CR26","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/icb.2008.56","volume":"86","author":"LC Pingel","year":"2008","unstructured":"Pingel, L. C. et al. Human beta-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response. Immunol Cell Biol \n                           86, 643\u2013649 (2008).","journal-title":"Immunol Cell Biol"},{"key":"623_CR27","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/j.0105-2896.2009.00866.x","volume":"234","author":"S Milling","year":"2010","unstructured":"Milling, S., Yrlid, U., Cerovic, V. & MacPherson, G. Subsets of migrating intestinal dendritic cells. Immunol Rev \n                           234, 259\u2013267 (2010).","journal-title":"Immunol Rev"},{"key":"623_CR28","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1007\/s10875-007-9112-0","volume":"27","author":"S Horiguchi","year":"2007","unstructured":"Horiguchi, S. et al. Migration of tumor antigen-pulsed dendritic cells after mucosal administration in the human upper respiratory tract. J Clin Immunol \n                           27, 598\u2013604 (2007).","journal-title":"J Clin Immunol"},{"key":"623_CR29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1471-2172-11-37","volume":"11","author":"L Yin","year":"2010","unstructured":"Yin, L. et al. Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria. BMC Immunol \n                           11, 37 (2010).","journal-title":"BMC Immunol"},{"key":"623_CR30","doi-asserted-by":"publisher","first-page":"3482","DOI":"10.4049\/jimmunol.173.5.3482","volume":"173","author":"CY Kao","year":"2004","unstructured":"Kao, C. Y. et al. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol \n                           173, 3482\u20133491 (2004).","journal-title":"J Immunol"},{"key":"623_CR31","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s10753-014-0083-z","volume":"38","author":"A Li","year":"2015","unstructured":"Li, A. et al. IL-22 Up-Regulates beta-Defensin-2 Expression in Human Alveolar Epithelium via STAT3 but Not NF-kappaB Signaling Pathway. Inflammation \n                           38, 1191\u20131200 (2015).","journal-title":"Inflammation"},{"key":"623_CR32","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1182\/blood-2011-01-331298","volume":"118","author":"N Caccamo","year":"2011","unstructured":"Caccamo, N. et al. Differentiation, phenotype, and function of interleukin-17-producing human Vgamma9Vdelta2 T cells. Blood \n                           118, 129\u2013138 (2011).","journal-title":"Blood"},{"key":"623_CR33","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/j.1749-6632.2011.06355.x","volume":"1247","author":"T Korn","year":"2012","unstructured":"Korn, T. & Petermann, F. Development and function of interleukin 17-producing gammadelta T cells. Ann N Y Acad Sci \n                           1247, 34\u201345 (2012).","journal-title":"Ann N Y Acad Sci"},{"key":"623_CR34","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nature11551","volume":"489","author":"CL Maynard","year":"2012","unstructured":"Maynard, C. L., Elson, C. O., Hatton, R. D. & Weaver, C. T. Reciprocal interactions of the intestinal microbiota and immune system. Nature \n                           489, 231\u2013241 (2012).","journal-title":"Nature"},{"key":"623_CR35","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1111\/j.1600-051X.2012.01914.x","volume":"39","author":"M Iniesta","year":"2012","unstructured":"Iniesta, M. et al. Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis. A randomized clinical trial. J Clin Periodontol \n                           39, 736\u2013744 (2012).","journal-title":"J Clin Periodontol"},{"key":"623_CR36","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1111\/jcpe.12155","volume":"40","author":"W Teughels","year":"2013","unstructured":"Teughels, W. et al. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol \n                           40, 1025\u20131035 (2013).","journal-title":"J Clin Periodontol"},{"key":"623_CR37","doi-asserted-by":"publisher","first-page":"2958","DOI":"10.1128\/IAI.01572-07","volume":"76","author":"Y Koizumi","year":"2008","unstructured":"Koizumi, Y., Kurita-Ochiai, T., Oguchi, S. & Yamamoto, M. Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P. gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice. Infect Immun \n                           76, 2958\u20132965 (2008).","journal-title":"Infect Immun"},{"key":"623_CR38","first-page":"494","volume":"97","author":"B Klausen","year":"1989","unstructured":"Klausen, B., Evans, R. T. & Sfintescu, C. Two complementary methods of assessing periodontal bone level in rats. Scand J Dent Res \n                           97, 494\u2013499 (1989).","journal-title":"Scand J Dent Res"},{"key":"623_CR39","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1128\/IAI.01502-07","volume":"76","author":"F Momoi","year":"2008","unstructured":"Momoi, F. et al. Nasal vaccination with the 40-kilodalton outer membrane protein of Porphyromonas gingivalis and a nontoxic chimeric enterotoxin adjuvant induces long-term protective immunity with reduced levels of immunoglobulin E antibodies. Infect Immun \n                           76, 2777\u20132784 (2008).","journal-title":"Infect Immun"},{"key":"623_CR40","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/j.1574-695X.2011.00895.x","volume":"64","author":"S Yuzawa","year":"2012","unstructured":"Yuzawa, S. et al. Sublingual vaccination with fusion protein consisting of the functional domain of hemagglutinin A of Porphyromonas gingivalis and Escherichia coli maltose-binding protein elicits protective immunity in the oral cavity. FEMS Immunol Med Microbiol \n                           64, 265\u2013272 (2012).","journal-title":"FEMS Immunol Med Microbiol"},{"key":"623_CR41","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1128\/AAC.01308-07","volume":"52","author":"K Hinrichsen","year":"2008","unstructured":"Hinrichsen, K. et al. Mouse beta-defensin-14, an antimicrobial ortholog of human beta-defensin-3. Antimicrob Agents Chemother \n                           52, 1876\u20131879 (2008).","journal-title":"Antimicrob Agents Chemother"},{"key":"623_CR42","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1159\/000265568","volume":"47","author":"T Maekawa","year":"2010","unstructured":"Maekawa, T. et al. Porphyromonas gingivalis antigens and interleukin-6 stimulate the production of monocyte chemoattractant protein-1 via the upregulation of early growth response-1 transcription in human coronary artery endothelial cells. J Vasc Res \n                           47, 346\u2013354 (2010).","journal-title":"J Vasc Res"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00623-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00623-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00623-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:19:22Z","timestamp":1671765562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00623-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,3]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["623"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-00623-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,3]]},"assertion":[{"value":"23 June 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Toshiya Kobayashi, F.S., and T.H. are employees of Megmilk Snow Brand Co., Ltd. R.K., M.Y. and Tomoko Kurita-Ochiai declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"545"}}