{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:46:09Z","timestamp":1782819969894,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The present study evaluated the protective effects of Oralis SB\u00ae (Osb), a commercial multi-strain probiotic formulation, in a ligature-induced experimental periodontitis (EPD) Sprague\u2013Dawley rat model. Male rats were subjected to ligature placement and orally administered Osb (1.25 \u00d7 108, 1.25 \u00d7 109, and 6.25 \u00d7 109 CFU\/head) or received single-strain treatments with each of the four constituent strains (1.25 \u00d7 109 CFU\/head) for 10 days. Periodontal changes were assessed by microbiological, biochemical, histological, and bone-related analyses. Ligature placement markedly increased anaerobic bacterial counts, neutrophil-associated myeloperoxidase activity, and inflammatory mediator production in gingival tissues, accompanied by elevated gingival IgA levels and impaired expression of epithelial tight junction-related genes, including claudin-1, claudin-5, occludin, and zonula occludens-1. Osb administration significantly attenuated bacterial overgrowth, restored gingival IgA contents, and suppressed the production of inflammatory mediators. Osb also reduced malondialdehyde level and inducible nitric oxide synthase activity, as markers of oxidative and nitrosative stress, and decreased metalloproteinase-8 expression in gingival tissue. In addition, Osb effectively prevented alveolar bone deterioration by improving focal bone mineral density, reducing osteoclast numbers, and restoring the receptor activator of nuclear factor-\u03baB\/osteoprotegerin balance. Histological evaluation further confirmed that Osb alleviated gingival inflammation and alveolar bone loss. Notably, the lowest dose of Osb (1.25 \u00d7 108 CFU\/head) consistently produced significantly greater protective effects than each of the four individual component strains across all measured parameters. Osb exerted protective effects against EPD by modulating anaerobic microbial overgrowth, inflammatory and oxidative responses, epithelial barrier integrity, and alveolar bone resorption. These findings support the therapeutic potential of Osb in periodontitis.<\/jats:p>","DOI":"10.3390\/antiox15070804","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects of Mixed Probiotics, Oralis SB\u00ae, on the Ligation-Induced Experimental Periodontitis and Alveolar Bone Loss in Rats"],"prefix":"10.3390","volume":"15","author":[{"given":"Su Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Hye","family":"Han","sequence":"additional","affiliation":[{"name":"Food Ingredients Research Team, R&D Center, Dong-A Pharmaceutical, Yongin 17073, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Su","family":"Park","sequence":"additional","affiliation":[{"name":"DENTIS Co., Ltd., Daegu 41065, Republic of Korea"},{"name":"Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1410-7688","authenticated-orcid":false,"given":"Jae-Kwang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-3804","authenticated-orcid":false,"given":"Sae-Kwang","family":"Ku","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nri3785","article-title":"Periodontitis: From microbial immune subversion to systemic inflammation","volume":"15","author":"Hajishengallis","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/prd.12313","article-title":"New developments in neutrophil biology and periodontitis","volume":"82","author":"Hajishengallis","year":"2000","journal-title":"Periodontology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ajem.2021.03.071","article-title":"Periodontal disease and myocardial infarction risk: A meta-analysis of cohort studies","volume":"48","author":"Qin","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102172","DOI":"10.1016\/j.jebdp.2025.102172","article-title":"The Association between Periodontal Disease and Stroke Risk: A Systematic Review and Meta-Analysis","volume":"25","author":"Zhang","year":"2025","journal-title":"J. Evid. Based Dent. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vitkov, L., Singh, J., Schauer, C., Minnich, B., Krunic, J., Oberthaler, H., Gamsjaeger, S., Herrmann, M., Knopf, J., and Hannig, M. (2023). Breaking the Gingival Barrier in Periodontitis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054544"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1651158","DOI":"10.1080\/21688370.2019.1651158","article-title":"Gingival epithelial barrier: Regulation by beneficial and harmful microbes","volume":"7","author":"Takahashi","year":"2019","journal-title":"Tissue Barriers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/j.1600-0722.2010.00782.x","article-title":"Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro","volume":"118","author":"Groeger","year":"2010","journal-title":"Eur. J. Oral Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1038\/ijos.2017.51","article-title":"Analysis of differential expression of tight junction proteins in cultured oral epithelial cells altered by Porphyromonas gingivalis, Porphyromonas gingivalis lipopolysaccharide, and extracellular adenosine triphosphate","volume":"10","author":"Guo","year":"2018","journal-title":"Int. J. Oral Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8823708","DOI":"10.1155\/2020\/8823708","article-title":"Anti-Early Stage of Bacterial Recolonization Effect of Curcuma longa Extract as Photodynamic Adjunctive Treatment","volume":"2020","author":"Hormdee","year":"2020","journal-title":"Int. J. Dent."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9187978","DOI":"10.1155\/2019\/9187978","article-title":"Antioxidants as Adjuvants in Periodontitis Treatment: A Systematic Review and Meta-Analysis","volume":"2019","author":"Castro","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Heta, S., and Robo, I. (2018). The Side Effects of the Most Commonly Used Group of Antibiotics in Periodontal Treatments. Med. Sci., 6.","DOI":"10.3390\/medsci6010006"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1600-051X.2010.01665.x","article-title":"Do probiotics offer opportunities to manipulate the periodontal oral microbiota?","volume":"38","author":"Teughels","year":"2011","journal-title":"J. Clin. Periodontol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jdent.2016.03.002","article-title":"Probiotics for managing caries and periodontitis: Systematic review and meta-analysis","volume":"48","author":"Gruner","year":"2016","journal-title":"J. Dent."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/jcpe.12545","article-title":"Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of chronic periodontitis: A systematic review and meta-analysis","volume":"43","author":"Davideau","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Blais, L., Auclair-Ouellet, N., Tremblay, A., and Binda, S. (2025). Effect of the Darolac((R)) (Oralis SB((R))) Probiotic Formulation on Oral Health: A Narrative Review. Microorganisms, 13.","DOI":"10.3390\/microorganisms13020408"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/idh.12589","article-title":"Probiotic mouthwash as an adjunct to mechanical therapy in the treatment of stage II periodontitis: A randomized controlled clinical trial","volume":"20","author":"Ranjith","year":"2022","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"320","DOI":"10.5005\/jp-journals-10024-3316","article-title":"Effects of Probiotics Mouthwash on Levels of Red Complex Bacteria in Chronic Periodontitis Patients: A Clinico-microbiological Study","volume":"23","author":"Tapashetti","year":"2022","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3746\/jkfn.2022.51.8.765","article-title":"Effects of Moringa oleifera L. and Eucommia ulmoides Oliver Mixed Formula on Ligation-Induced Experimental Periodontitis and Alveolar Bone Loss in Rats","volume":"51","author":"Kim","year":"2022","journal-title":"J. Korean Soc. Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Park, S.-I., Kang, S.-J., Han, C.-H., Kim, J.-W., Song, C.-H., Lee, S.-N., Ku, S.-K., and Lee, Y.-J. (2016). The Effects of Topical Application of Polycal (a 2:98 (g\/g) Mixture of Polycan and Calcium Gluconate) on Experimental Periodontitis and Alveolar Bone Loss in Rats. Molecules, 21.","DOI":"10.3390\/molecules21040527"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0891-5849(97)00280-3","article-title":"Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation","volume":"24","author":"Cuzzocrea","year":"1998","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1902\/jop.2005.76.11.1901","article-title":"Effect of sodium alendronate on alveolar bone resorption in experimental periodontitis in rats","volume":"76","author":"Menezes","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Canut-Delgado, N., Giovannoni, M.L., and Chimenos-Kustner, E. (2021). Are probiotics a possible treatment of periodontitis? Probiotics against periodontal disease: A systematic review. Br. Dent. J., online ahead of print.","DOI":"10.1038\/s41415-021-3624-5"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1128\/MMBR.62.1.71-109.1998","article-title":"Oral microbial ecology and the role of salivary immunoglobulin A","volume":"62","author":"Marcotte","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5005\/jp-journals-10024-1114","article-title":"Salivary immunoglobulin classes in Nigerians with periodontitis","volume":"13","author":"Olayanju","year":"2012","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"226","DOI":"10.18794\/aams\/196874","article-title":"Role of salivary immunoglobulins in oral health: Investigating levels of IgA and IgG in saliva and their impact on periodontal disease among patients in Peshawar, Pakistan","volume":"79","author":"Zuhair","year":"2025","journal-title":"Ann. Acad. Medicae Silesiensis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/prd.12342","article-title":"Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way","volume":"84","author":"Sczepanik","year":"2000","journal-title":"Periodontology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1600-0757.2006.00178.x","article-title":"The role of reactive oxygen and antioxidant species in periodontal tissue destruction","volume":"43","author":"Chapple","year":"2007","journal-title":"Periodontol. 2000"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1902\/jop.2010.100196","article-title":"Associations between matrix metalloproteinase-8 and -14 and myeloperoxidase in gingival crevicular fluid from subjects with progressive chronic periodontitis: A longitudinal study","volume":"81","author":"Hernandez","year":"2010","journal-title":"J. Periodontol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/jre.12211","article-title":"Quantifying oral inflammatory load: Oral neutrophil counts in periodontal health and disease","volume":"50","author":"Landzberg","year":"2015","journal-title":"J. Periodontal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1128\/IAI.67.5.2319-2326.1999","article-title":"Activation of neutrophil collagenase in periodontitis","volume":"67","author":"Romanelli","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_32","first-page":"474","article-title":"Role of Matrix Metalloproteinases in Human Periodontal-Diseases","volume":"64","author":"Birkedalhansen","year":"1993","journal-title":"J. Periodontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1128\/IAI.70.5.2512-2518.2002","article-title":"Hydrolysis of epithelial junctional proteins by Porphyromonas gingivalis gingipains","volume":"70","author":"Katz","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hernandez-Rios, P., Pussinen, P.J., Vernal, R., and Hernandez, M. (2017). Oxidative Stress in the Local and Systemic Events of Apical Periodontitis. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00869"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6014706","DOI":"10.1155\/2023\/6014706","article-title":"Assessment of Oxidative Stress by the Estimation of Lipid Peroxidation Marker Malondialdehyde (MDA) in Patients with Chronic Periodontitis: A Systematic Review and Meta-Analysis","volume":"2023","author":"Mohideen","year":"2023","journal-title":"Int. J. Dent."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1600-0765.2005.00818.x","article-title":"Lipid peroxidation: A possible role in the induction and progression of chronic periodontitis","volume":"40","author":"Tsai","year":"2005","journal-title":"J. Periodontal Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41368-019-0068-8","article-title":"Interleukin-1\u03b2 is a potential therapeutic target for periodontitis: A narrative review","volume":"12","author":"Cheng","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1902\/jop.2008.080183","article-title":"Cytokines that promote periodontal tissue destruction","volume":"79","author":"Graves","year":"2008","journal-title":"J. Periodontol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1177\/00220345010800100301","article-title":"Tumor necrosis factor modulates fibroblast apoptosis, PMN recruitment, and osteoclast formation in response to P. gingivalis infection","volume":"80","author":"Graves","year":"2001","journal-title":"J. Dent. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1902\/jop.1992.63.5.405","article-title":"Effect of exogenously applied prostaglandin E2 on alveolar bone loss\u2014Histometric analysis","volume":"63","author":"Miyauchi","year":"1992","journal-title":"J. Periodontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1902\/jop.2007.070073","article-title":"RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis","volume":"78","author":"Jin","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tomina, D.C., Petrutiu, S.A., Dinu, C.M., Crisan, B., Cighi, V.S., and Ratiu, I.A. (2022). Comparative Testing of Two Ligature-Induced Periodontitis Models in Rats: A Clinical, Histological and Biochemical Study. Biology, 11.","DOI":"10.3390\/biology11050634"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/7\/804\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:59:25Z","timestamp":1782817165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/7\/804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,27]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["antiox15070804"],"URL":"https:\/\/doi.org\/10.3390\/antiox15070804","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,27]]}}}