{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:59:55Z","timestamp":1790762395522,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K11094"],"award-info":[{"award-number":["18K11094"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K17918"],"award-info":[{"award-number":["18K17918"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["19K08361"],"award-info":[{"award-number":["19K08361"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20H04119"],"award-info":[{"award-number":["20H04119"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20K11644"],"award-info":[{"award-number":["20K11644"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Exercise can be hypothesized to play an important role in non-alcoholic fatty liver disease (NAFLD) treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n = 49) or dietary restriction (n = 21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and, measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in the clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher, and that of Prevotella (\u221228.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.<\/jats:p>","DOI":"10.3390\/ijerph18073470","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T13:17:53Z","timestamp":1616764673000},"page":"3470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Effects of Exercise on the Oral Microbiota and Saliva of Patients with Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Fumihiko","family":"Uchida","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of Tsukuba Hospital, Tsukuba, Ibaraki 305-8576, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sechang","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shida","sequence":"additional","affiliation":[{"name":"Department of Medical Technology and Sciences, International University of Health and Welfare, Narita, Chiba 286-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-7449","authenticated-orcid":false,"given":"Hideo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7231-7478","authenticated-orcid":false,"given":"Kenji","family":"Yamagata","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Bukawa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoji","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Shoda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/idj.12264","article-title":"Periodontal disease and the metabolic syndrome","volume":"67","author":"Lamster","year":"2017","journal-title":"Int. Dent. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1177\/0022034510376542","article-title":"Metabolic syndrome, periodontal infection, and dental caries","volume":"89","author":"Timonen","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.archoralbio.2014.05.003","article-title":"Periodontal disease and metabolic syndrome: A qualitative critical review of their association","volume":"59","author":"Watanabe","year":"2014","journal-title":"Arch. Oral Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s00535-012-0533-z","article-title":"Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: A multicenter large retrospective study","volume":"47","author":"Eguchi","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yoneda, M., Naka, S., Nakano, K., Wada, K., Endo, H., Mawatari, H., Imajo, K., Nomura, R., Hokamura, K., and Ono, M. (2012). Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease. BMC Gastroenterol., 12.","DOI":"10.1186\/1471-230X-12-16"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1038\/s41598-020-60904-8","article-title":"Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation","volume":"10","author":"Nagasaki","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nakajima, M., Arimatsu, K., Kato, T., Matsuda, Y., Minagawa, T., Takahashi, N., Ohno, H., and Yamazaki, K. (2015). Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134234"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/hep.23129","article-title":"Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss","volume":"50","author":"Johnson","year":"2009","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/hep.23276","article-title":"Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis","volume":"51","author":"Promrat","year":"2010","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/oby.2009.274","article-title":"A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents","volume":"18","author":"Wang","year":"2010","journal-title":"Obesity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/j.1365-2036.2009.04122.x","article-title":"Clinical trial: A nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease","volume":"30","year":"2009","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.jdent.2005.01.004","article-title":"Increased physical activity reduces prevalence of periodontitis","volume":"33","author":"Borawski","year":"2005","journal-title":"J. Dent."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1902\/jop.2005.76.8.1362","article-title":"Periodontitis and three health-enhancing behaviors: Maintaining normal weight, engaging in recommended level of exercise, and consuming a high-quality diet","volume":"76","author":"Borawski","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1600-0765.2010.01314.x","article-title":"The association between periodontal disease, physical activity and healthy diet among adults in Jordan","volume":"46","author":"Bawadi","year":"2011","journal-title":"J. Periodontal. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1023\/A:1025622815579","article-title":"Increased physical activity decreases periodontitis risk in men","volume":"18","author":"Merchant","year":"2003","journal-title":"Eur. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/hep.27544","article-title":"Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: A retrospective study","volume":"61","author":"Oh","year":"2015","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43029","DOI":"10.1038\/srep43029","article-title":"High-Intensity Aerobic Exercise Improves Both Hepatic Fat Content and Stiffness in Sedentary Obese Men with Nonalcoholic Fatty Liver Disease","volume":"7","author":"Oh","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1249\/MSS.0b013e31829afc33","article-title":"Exercise reduces inflammation and oxidative stress in obesity-related liver diseases","volume":"45","author":"Oh","year":"2013","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"565","DOI":"10.2147\/TCRM.S153397","article-title":"Exercise habituation is effective for improvement of periodontal disease status: A prospective intervention study","volume":"14","author":"Omori","year":"2018","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11977","DOI":"10.1038\/s41598-017-12358-8","article-title":"Exercise training enhances in vivo clearance of endotoxin and attenuates inflammatory responses by potentiating Kupffer cell phagocytosis","volume":"7","author":"Komine","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/j.1440-1746.2007.05001.x","article-title":"Non-alcoholic fatty liver disease in the Asia-Pacific region: Definitions and overview of proposed guidelines","volume":"22","author":"Chitturi","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/j.1440-1746.2007.05002.x","article-title":"Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: Executive summary","volume":"22","author":"Farrell","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1089\/met.2013.0143","article-title":"Regular exercise coupled to diet regimen accelerates reduction of hepatic steatosis and associated pathological conditions in nonalcoholic fatty liver disease","volume":"12","author":"Oh","year":"2014","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nbt.2676","article-title":"Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences","volume":"31","author":"Langille","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D199","DOI":"10.1093\/nar\/gkt1076","article-title":"Data, information, knowledge and principle: Back to metabolism in KEGG","volume":"42","author":"Kanehisa","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00535-017-1377-3","article-title":"Skeletal muscle mass to visceral fat area ratio is an important determinant affecting hepatic conditions of non-alcoholic fatty liver disease","volume":"53","author":"Shida","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cmet.2012.05.012","article-title":"Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling","volume":"16","author":"Imajo","year":"2012","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1538\/expanim.17-0112","article-title":"Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis","volume":"67","author":"Akiyama","year":"2018","journal-title":"Exp. Anim."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1139\/o2012-016","article-title":"Lactoferrin, a bird\u2019s eye view","volume":"90","author":"Vogel","year":"2012","journal-title":"Biochem. Cell Biol."},{"key":"ref_32","first-page":"927","article-title":"Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: Comparison with other neutrophil-derived proteins","volume":"91","author":"Sugi","year":"1996","journal-title":"Am. J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1600-0765.2012.01479.x","article-title":"Elevated levels of salivary lactoferrin, a marker for chronic periodontitis?","volume":"47","author":"Glimvall","year":"2012","journal-title":"J. Periodontal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/ibd.21866","article-title":"Role of the microbiota in inflammatory bowel diseases","volume":"18","author":"Nagalingam","year":"2012","journal-title":"Inflamm. Bowel Dis."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/7\/3470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:32:53Z","timestamp":1760362373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/7\/3470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,26]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijerph18073470"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18073470","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,26]]}}}