{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:30:58Z","timestamp":1793208658944,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1\u03b2 (IL-1\u03b2) by 39.31% (p &lt; 0.01), 17.26% (p &lt; 0.05), and 14.74% (p &lt; 0.05), respectively, whereas the PP group showed decreases of 34.79% (p &lt; 0.05), 29.85% (p &lt; 0.01), and 19.74% (p &lt; 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p &lt; 0.05) and increased bone volume fraction (BV\/TV) by 49.5% (p &lt; 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p &lt; 0.05), it resulted in a 40.4% improvement in BV\/TV (p &gt; 0.05). Histological assessments via hematoxylin and eosin (H&amp;E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats.<\/jats:p>","DOI":"10.3390\/microorganisms13071701","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:56:14Z","timestamp":1753084574000},"page":"1701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of Live Ligilactobacillus salivarius CCFM1332 and Its Postbiotics on Porphyromonas gingivalis Colonization, Alveolar Bone Resorption and Inflammation in a Rat Model of Periodontitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7809-3476","authenticated-orcid":false,"given":"Qing","family":"Hong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai 200436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyong","family":"Mao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-2214","authenticated-orcid":false,"given":"Qiuxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumao","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai 200436, China"},{"name":"State Key Laboratory of Food Science and resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3777-087X","authenticated-orcid":false,"given":"Zhenmin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai 200436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/jemt.23101","article-title":"Characterization of ligature-induced experimental periodontitis","volume":"81","author":"Park","year":"2018","journal-title":"Microsc. Res. Tech."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/jre.12615","article-title":"A novel IkB kinase inhibitor attenuates ligature-induced periodontal disease in mice","volume":"54","author":"Kure","year":"2019","journal-title":"J. Periodontal Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/jcpe.13506","article-title":"Global, regional, and national burden of severe periodontitis, 1990\u20132019: An analysis of the Global Burden of Disease Study 2019","volume":"48","author":"Chen","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1111\/jcpe.14022","article-title":"Low energy intake and nutritional maladaptation in terminal stage IV periodontitis","volume":"51","author":"Liu","year":"2024","journal-title":"J. Clin. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/jre.13337","article-title":"Burden of severe periodontitis and edentulism in 2021, with projections up to 2050: The Global Burden of Disease 2021 study","volume":"59","author":"Nascimento","year":"2024","journal-title":"J. Periodontal Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1902\/jop.2007.060301","article-title":"Periodontal destruction is associated with coronary artery disease and periodontal infection with acute coronary syndrome","volume":"78","author":"Gotsman","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/1040841X.2020.1724872","article-title":"Exploring the putative interactions between chronic kidney disease and chronic periodontitis","volume":"46","author":"Hickey","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.chom.2014.05.012","article-title":"Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis","volume":"15","author":"Maekawa","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.4049\/jimmunol.0900378","article-title":"TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88 independent, whereas MyD88 is required to clear infection","volume":"184","author":"Burns","year":"2010","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17038","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1002\/jbmr.2827","article-title":"Rheumatoid arthritis exacerbates the severity of osteonecrosis of the jaws (ONJ) in mice. A randomized, prospective, controlled animal study","volume":"31","author":"Hsu","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/prd.12002","article-title":"Inflammatory and immune pathways in the pathogenesis of periodontal disease","volume":"64","author":"Cekici","year":"2014","journal-title":"Periodontol 2000"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/jcpe.13230","article-title":"Adjunctive effect of locally delivered antimicrobials in periodontitis therapy: A systematic review and meta-analysis","volume":"47","author":"Herrera","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/jcpe.13290","article-title":"Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline","volume":"47","author":"Sanz","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"978","DOI":"10.14219\/jada.archive.2009.0307","article-title":"Periodontitis: An archetypical biofilm disease","volume":"140","author":"Schaudinn","year":"2009","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-96881-6_1","article-title":"Advances in experimental research about periodontitis: Lessons from the past, ideas for the future","volume":"1373","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Butera, A., Folini, E., Cosola, S., Russo, G., Scribante, A., Gallo, S., Stablum, G., Menchini Fabris, G.B., Covani, U., and Genovesi, A. (2023). Evaluation of the Efficacy of Probiotics Domiciliary Protocols for the Management of Periodontal Disease, in Adjunction of Non-Surgical Periodontal Therapy (NSPT): A Systematic Literature Review. Appl. Sci., 13.","DOI":"10.3390\/app13010663"},{"key":"ref_18","first-page":"e51177","article-title":"Clinical implications of probiotics in oral and periodontal health: A comprehensive review","volume":"15","author":"Shirbhate","year":"2023","journal-title":"Cureus"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Homayouni Rad, A., Pourjafar, H., and Mirzakhani, E. (2023). A comprehensive review of the application of probiotics and postbiotics in oral health. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1120995"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kainulainen, V., Tang, Y., Spillmann, T., Kilpinen, S., Reunanen, J., Saris, P.E., and Satokari, R. (2015). The canine isolate Lactobacillus acidophilus LAB20 adheres to intestinal epithelium and attenuates LPS-induced IL-8 secretion of enterocytes in vitro. BMC Microbiol., 15.","DOI":"10.1186\/s12866-014-0337-9"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/14787210.2016.1194198","article-title":"The role of probiotic bacteria in managing periodontal disease: A systematic review","volume":"14","author":"Matsubara","year":"2016","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_22","first-page":"381","article-title":"Lactobacillus reuteri for chronic periodontitis: Focus on underlying mechanisms and future perspectives","volume":"40","author":"Zhou","year":"2024","journal-title":"Biotechnol. Genet. Eng. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, R., He, Q., Hu, Q., Yang, J., and Tang, X. (Probiotics Antimicrob. Proteins, 2024). Assessment of the effectiveness of probiotics-assisted physical interventions in the management of chronic periodontitis: A randomized controlled clinical trial, Probiotics Antimicrob. Proteins, prepublish.","DOI":"10.1007\/s12602-024-10369-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1111\/odi.14739","article-title":"Lactobacillus fermentum attenuates the alveolar bone loss in ligature-induced periodontitis in mice","volume":"30","author":"Lee","year":"2024","journal-title":"Oral Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"D\u2019Agostino, S., Valentini, G., Iarussi, F., and Dolci, M. (2024). Effect of Probiotics Lactobacillus rhamnosus and Lactobacillus plantarum on caries and periodontal diseases: A systematic review. Dent. J., 12.","DOI":"10.3390\/dj12040102"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Karaca, B., Yilmaz, M., and Gursoy, U.K. (2022). Targeting Nrf2 with probiotics and postbiotics in the treatment of periodontitis. Biomolecules, 12.","DOI":"10.3390\/biom12050729"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Moraes, R.M., Schlagenhauf, U., and Anbinder, A.L. (2022). Outside the limits of bacterial viability: Postbiotics in the management of periodontitis. Biochem. Pharmacol., 201.","DOI":"10.1016\/j.bcp.2022.115072"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"\u017b\u00f3\u0142kiewicz, J., Marzec, A., Ruszczy\u0144ski, M., and Feleszko, W. (2020). Postbiotics-a step beyond pre- and probiotics. Nutrients, 12.","DOI":"10.3390\/nu12082189"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tifs.2018.03.009","article-title":"Postbiotics: An evolving term within the functional foods field","volume":"75","author":"Garcia","year":"2018","journal-title":"Trends Food Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5283","DOI":"10.1007\/s00253-020-10503-4","article-title":"Anti-Salmonella mode of action of natural L-phenyl lactic acid purified from Lactobacillus plantarum ZJ316","volume":"104","author":"Zhou","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1039\/D2FO02938C","article-title":"Evaluation of heat-inactivated Limosilactobacillus fermentum CCFM1139 and its supernatant for the relief of experimental periodontitis in rats","volume":"14","author":"Ye","year":"2023","journal-title":"Food Funct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1128\/JB.182.5.1374-1382.2000","article-title":"Streptococcus gordonii biofilm formation: Identification of genes that code for biofilm phenotypes","volume":"182","author":"Loo","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1039\/D1FO00409C","article-title":"Effects of Limosilactobacillus fermentum CCFM1139 on experimental periodontitis in rats","volume":"12","author":"Zhang","year":"2021","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1902\/jop.1967.38.6.610","article-title":"The Gingival Index, the Plaque Index and the Retention Index Systems","volume":"38","year":"1967","journal-title":"J. Periodontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"326","DOI":"10.4103\/0974-8490.138287","article-title":"Evaluation of the efficacy of 2% curcumin gel in the treatment of experimental periodontitis","volume":"6","author":"Hosadurga","year":"2014","journal-title":"Pharmacogn. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.1039\/C8FO01303A","article-title":"Effects of an ethanol extract from Lactobacillus paracasei subsp. paracasei NTU 101 fermented skimmed milk on lipopolysaccharide-induced periodontal \ninflammation in rats","volume":"9","author":"Liu","year":"2018","journal-title":"Food Funct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1600-0765.2007.00989.x","article-title":"Protective effects of baicalin on ligature-induced periodontitis in rats","volume":"43","author":"Cai","year":"2008","journal-title":"J. Periodontal Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/JPER.16-0435","article-title":"Experimental periodontitis in Msx2 mutant mice induces alveolar bone necrosis","volume":"91","author":"Korah","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jiang, L., Ma, Y., Xiong, Y., Tan, Y., Duan, X., Liao, X., and Wang, J. (2022). Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism. Front. Chem., 10.","DOI":"10.3389\/fchem.2022.1035741"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s12275-022-1514-4","article-title":"The rationale and potential for using Lactobacillus in the management of periodontitis","volume":"60","author":"Wang","year":"2022","journal-title":"J. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, H.Y., Lin, L., Fu, W., Yu, H.Y., Yu, N., Tan, L.S., Cheng, J.W., and Pan, Y.P. (2017). Preventive effects of the novel antimicrobial peptide Nal-P-113 in a rat periodontitis model by limiting the growth of Porphyromonas gingivalis and modulating IL-1\u03b2 and TNF-\u03b1 production. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1931-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kobayashi, R., Kobayashi, T., Sakai, F., Hosoya, T., Yamamoto, M., and Kurita-Ochiai, T. (2017). Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-00623-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/omi.12330","article-title":"Lactobacilli postbiotics reduce biofilm formation and alter transcription of virulence genes of Aggregatibacter actinomycetemcomitans","volume":"36","author":"Ishikawa","year":"2021","journal-title":"Mol. Oral Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Jung, J.I., Baek, S.M., Nguyen, T.H., Kim, J.W., Kang, C.H., Kim, S., and Imm, J.Y. (2021). Effects of probiotic culture supernatant on cariogenic biofilm formation and RANKL-induced osteoclastogenesis in RAW 264.7 macrophages. Molecules, 26.","DOI":"10.3390\/molecules26030733"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yang, K.M., Kim, J.S., Kim, H.S., Kim, Y.Y., Oh, J.K., Jung, H.W., Park, D.S., and Bae, K.H. (2021). Lactobacillus reuteri AN417 cell-free culture supernatant as a novel antibacterial agent targeting oral pathogenic bacteria. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80921-x"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.imlet.2011.05.007","article-title":"Upregulation of heme oxygenase-1 via PI3K\/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages","volume":"139","author":"Park","year":"2011","journal-title":"Immunol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jiang, H., Zhang, Y., Xiong, X., Harville, E.W., O, K., and Qian, X. (2016). Salivary and serum inflammatory mediators among pre-conception women with periodontal disease. BMC Oral Health, 16.","DOI":"10.1186\/s12903-016-0306-9"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/JPER.18-0466","article-title":"Dysregulation of miR-146a by periodontal pathogens: A risk for acute coronary syndrome","volume":"90","author":"George","year":"2019","journal-title":"J. Periodontol."},{"key":"ref_51","first-page":"2214","article-title":"Inflammatory cytokine levels in patients with periodontitis and\/or coronary heart disease","volume":"8","author":"Zhu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"509","DOI":"10.4103\/0972-124X.201694","article-title":"Tumor necrosis factor-\u03b1, interleukin-4 and -6 in the serum of health, chronic periodontitis, and type 2 diabetes mellitus","volume":"20","author":"Acharya","year":"2016","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/jcla.21917","article-title":"Correlation of serum and salivary cytokines level with clinical parameters in metabolic syndrome with periodontitis","volume":"30","author":"Chauhan","year":"2016","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1007\/s00011-014-0776-7","article-title":"Clinical associations between IL-17 family cytokines and periodontitis and potential differential roles for IL-17A and IL-17E in periodontal immunity","volume":"63","author":"Awang","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_55","first-page":"846052","article-title":"Association between polymorphisms in interleukin-17A and -17F genes and chronic periodontal disease","volume":"2012","author":"Madeira","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_56","first-page":"170","article-title":"Detection of IL-4, IL-6 and IL-12 serum levels in generalized aggressive periodontitis","volume":"8","author":"Robati","year":"2011","journal-title":"Iran. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00784-018-2471-5","article-title":"The ratios of pro-inflammatory to anti-inflammatory cytokines in the serum of chronic periodontitis patients with and without type 2 diabetes and\/or smoking habit","volume":"23","author":"Miranda","year":"2019","journal-title":"Clin. Oral Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1902\/jop.2013.130117","article-title":"Saliva and serum levels of B-cell activating factors and tumor necrosis factor-\u03b1 in patients with periodontitis","volume":"85","author":"Nizam","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nie, Q., Wan, X., Tao, H., Yang, Q., Zhao, X., Liu, H., Hu, J., Luo, Y., Shu, T., and Geng, R. (2023). Multi-function screening of probiotics to improve oral health and evaluating their efficacy in a rat periodontitis model. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1261189"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e6932","DOI":"10.1097\/MD.0000000000006932","article-title":"Association between interleukin-8 levels and chronic periodontal disease: A PRISMA-compliant systematic review and meta-analysis","volume":"96","author":"Finoti","year":"2017","journal-title":"Medicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s10266-019-00470-2","article-title":"IL-10 secreting B cells regulate periodontal immune response during periodontitis","volume":"108","author":"Shi","year":"2020","journal-title":"Odontology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1492069","DOI":"10.1155\/ijod\/1492069","article-title":"Insights Into the Mechanism of Action of Chlorhexidine on Porphyromonas gingivalis","volume":"2025","year":"2025","journal-title":"Int. J. Dent."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1600-0765.1991.tb01650.x","article-title":"Immunologic mechanisms of pathogenesis in periodontal diseases: An assessment","volume":"26","author":"Ranney","year":"1991","journal-title":"J. Periodontal Res."},{"key":"ref_64","unstructured":"Robert, J.G., and Ray, C.W. Overview of periodontal disease: Causes, pathogenesis, and characteristics. Periodontal Disease and Overall Health: A Clinician\u2032s Guide, Professional Audience Communications, Inc.. [2nd ed.]."},{"key":"ref_65","first-page":"315","article-title":"Effect of oral Lactobacillus salivarius TI2711 (LS1) administration on periodontopathic bacteria in subgingival plaque","volume":"48","author":"Matsuoka","year":"2006","journal-title":"J. Jpn. Soc. Periodontal Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4049\/jimmunol.160.1.403","article-title":"IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis","volume":"160","author":"Assuma","year":"1998","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrd3669","article-title":"Inflammatory bone loss: Pathogenesis and therapeutic intervention","volume":"11","author":"Redlich","year":"2012","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lap\u00e9rine, O., Cloitre, A., Caillon, J., Huck, O., Bugueno, I.M., Pilet, P., Sourice, S., Le Tilly, E., Palmer, G., and Davideau, J.L. (2016). Interleukin-33 and RANK-L interplay in the alveolar bone loss associated to periodontitis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168080"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"615486","DOI":"10.1155\/2015\/615486","article-title":"Mechanisms of bone resorption in periodontitis","volume":"2015","author":"Hienz","year":"2015","journal-title":"J. Immunol. Res."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/7\/1701\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:12:51Z","timestamp":1760033571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/7\/1701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,20]]},"references-count":69,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["microorganisms13071701"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13071701","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,20]]}}}