{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:45:47Z","timestamp":1788018347127,"version":"build-2784847793"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Trade, Industry &amp; Energy (MOTIE, Republic of Korea)","award":["20008991"],"award-info":[{"award-number":["20008991"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The purpose of this study is to evaluate Lactobacillus paracasei SMB092 as a prophylactic agent for oral pathogens. We examined the physical interaction of SMB092 with a host by identifying the presence of mucus-binding (MuB) protein domains and the capacity of the mucin binding. We determined the role of heat-killed SMB092 in host oral immunity by quantifying the mRNA levels of \u03b2-defensins (BDs), Toll-like receptors (TLRs), and their cofactors (CD14\/CD36) in normal human oral keratinocytes (HOK-16B cells). To assess the clinically relevant oral health effects of heat-killed SMB092, the growth of Porphyromonas (P.) gingivalis and the production of a volatile sulfur compound (H2S) were also measured in the filtered condition media (FCM) obtained from its cultures with HOK-16B cells. SMB092 possessed 14 putative MuB protein domains and was attached to mucin. Significant amounts of hBD1\/2 and TLR2\/6 were expressed in heat-killed SMB092-treated HOK-16B cells. The specific neutralization of TLR2 attenuated the expression of hBD1\/2 and CD14\/CD36. The FCM inhibited the growth of P. gingivalis and the production of H2S. Our data indicate that heat-killed SMB092 may contribute to a healthy oral microbiome as an immune stimulant in the production of BDs via the activation of the TLR2\/6 signaling pathway.<\/jats:p>","DOI":"10.3390\/microorganisms12112147","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:51:29Z","timestamp":1729842689000},"page":"2147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heat-Killed Lactobacillus paracasei SMB092 Reduces Halitosis by Stimulating the Expression of \u03b2-Defensins in Oral Keratinocytes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3554-8984","authenticated-orcid":false,"given":"Won-Ju","family":"Kim","sequence":"first","affiliation":[{"name":"Sempio Foods Company, R&D Center, Cheongju 28156, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyubin","family":"Jung","sequence":"additional","affiliation":[{"name":"Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taewook","family":"Kim","sequence":"additional","affiliation":[{"name":"CJ Bioscience Inc., Seoul 04527, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinseon","family":"Kim","sequence":"additional","affiliation":[{"name":"Sempio Foods Company, R&D Center, Cheongju 28156, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Serk","family":"Hurh","sequence":"additional","affiliation":[{"name":"Sempio Foods Company, R&D Center, Cheongju 28156, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6463-756X","authenticated-orcid":false,"given":"Hangeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Research and Development Center, Skin Biotechnology Center Co., Ltd., Yongin 17104, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Yu","family":"Soung","sequence":"additional","affiliation":[{"name":"Sempio Foods Company, R&D Center, Cheongju 28156, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.4103\/INJO.INJO_20_23","article-title":"A study to assess the unique oral health challenges faced by elderly individuals, including denture use, dry mouth, and periodontal diseases","volume":"11","author":"Chavda","year":"2023","journal-title":"Int. J. Oral Care Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1399-302X.2009.00544.x","article-title":"Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque","volume":"24","author":"Byrne","year":"2009","journal-title":"Oral Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hajishengallis, G., Kajikawa, T., Hajishengallis, E., Maekawa, T., Reis, E.S., Mastellos, D.C., Tancopoulou, D., Hasturk, H., and Lambris, J.D. (2019). Complement-dependent mechanisms and interventions in periodontal disease. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00406"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100887","DOI":"10.1016\/j.nmni.2021.100887","article-title":"Alleviation of halitosis by use of probiotics and their protective mechanisms in the oral cavity","volume":"42","author":"Karbalaei","year":"2021","journal-title":"New Microbes New Infect."},{"key":"ref_5","first-page":"249","article-title":"Antimicorbial effect of Zea mays L. and Magnoliae cortex extract mixtures on periodontal pathogen and effect on human gingival fibrobla","volume":"32","author":"Kim","year":"2002","journal-title":"J. Periodont. Implant Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lim, H.S., Yeu, J.E., Hong, S.P., and Kang, M.S. (2018). Characterization of Antibacterial cell-free supernatant from oral care probiotic Weissella cibaria, CMU. Molecules, 23.","DOI":"10.3390\/molecules23081984"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/lam.13275","article-title":"Antibacterial activity of viable and heat-killed probiotic strains against oral pathogens","volume":"70","author":"Chen","year":"2020","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.micpath.2018.07.032","article-title":"Inhibitory effect of probiotic Lactobacillus supernatants from the oral cavity on Streptococcus mutans biofilms","volume":"123","author":"Rossoni","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3390\/nu3050613","article-title":"Lactobacillus adhesion to mucus","volume":"3","author":"Miller","year":"2011","journal-title":"Nutrients"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.1097\/MCG.0b013e318227414a","article-title":"Impact of probiotics on colonizing microbiota of the gut","volume":"45","author":"Sanders","year":"2011","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3920\/BM2013.0061","article-title":"Heat-killed probiotic bacteria differentially regulate colonic epithelial cell production of human \u03b2-defensin-2: Dependence on inflammatory cytokines","volume":"5","author":"Habil","year":"2014","journal-title":"Benef. Microbes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/jcpe.13084","article-title":"The guardians of the periodontium-sequential and differential expression of antimicrobial peptides during gingival inflammation. Results from in vivo and in vitro studies","volume":"46","author":"Dommisch","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Siciliano, R.A., Reale, A., Mazzeo, M.F., Morandi, S., Silvetti, T., and Brasca, M. (2021). Parabiotics: A new perspective for functional foods and nutraceuticals. Nutrients, 13.","DOI":"10.3390\/nu13041225"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hyatt, D., Chen, G.L., LoCascio, P.F., Land, M.L., Larimer, F.W., and Hauser, L.J. (2010). Prodigal: Prokaryotic gene recognition and translation initiation site identification. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-119"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"W686","DOI":"10.1093\/nar\/gki366","article-title":"The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and snoRNAs","volume":"33","author":"Schattner","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D130","DOI":"10.1093\/nar\/gku1063","article-title":"Rfam 12.0: Updates to the RNA families database","volume":"43","author":"Nawrocki","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Edgar, R.C. (2007). PILER-CR: Fast and accurate identification of CRISPR repeats. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-18"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bland, C., Ramsey, T.L., Sabree, F., Lowe, M., Brown, K., Kyrpides, N.C., and Hugenholtz, P. (2007). CRISPR Recognition Tool (CRT): A tool for automatic detection of clustered regularly interspaced palindromic repeats. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-209"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D231","DOI":"10.1093\/nar\/gkt1253","article-title":"EggNOG v4.0: Nested orthology inference across 3686 organisms","volume":"42","author":"Powell","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium (2015). UniProt: A hub for protein information. Nucleic Acids Res., 43, D204\u2013D212.","DOI":"10.1093\/nar\/gku989"},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1093\/nar\/gki866","article-title":"The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes","volume":"33","author":"Overbeek","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/cr.2009.6","article-title":"DOG 1.0: Illustrator of Protein Domain Structures","volume":"19","author":"Ren","year":"2009","journal-title":"Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Karbowiak, M., Galek, M., Szydlowska, A., and Zieli\u0144ska, D. (2022). The influence of the degree of thermal inactivation of probiotic lactic acid bacteria and their postbiotics on aggregation and adhesion inhibition of selected pathogens. Pathogens, 11.","DOI":"10.3390\/pathogens11111260"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1128\/IAI.00449-08","article-title":"Toll-like receptor 2 and NALP2 mediate induction of human beta-defensin by Fusobacterium nucleatum in gingival epithelial cells","volume":"77","author":"Ji","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s12602-022-09949-x","article-title":"Levilactobacillus brevis KU15151 inhibits Staphylococcus aureus lipoteichoic acid-induced inflammation in RAW 264.7 macrophages","volume":"14","author":"Kim","year":"2022","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nguyen, A.T., Kim, M., Kim, Y.E., Kim, H., Lee, S., Lee, Y., and Kim, K.Y. (2023). MSF enhances human antimicrobial peptide \u03b2-defensin (HBD2 and HBD3) expression and attenuates inflammation via the NF-\u03baB and p38 signaling pathways. Molecules, 28.","DOI":"10.3390\/molecules28062744"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1128\/JVI.00174-13","article-title":"Hepatitis C Virus suppresses C9 complement synthesis and impairs membrane attack complex function","volume":"87","author":"Kim","year":"2013","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1600-051X.2006.00893.x","article-title":"Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds","volume":"33","author":"Kang","year":"2006","journal-title":"J. Clin. Periodontol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1146\/annurev-food-030212-182700","article-title":"The secretion, components, and properties of saliva","volume":"4","author":"Carpenter","year":"2013","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrmicro2297","article-title":"Host interactions of probiotic bacterial surface molecules: Comparison with commensals and pathogens","volume":"8","author":"Lebeer","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.12938\/bmfh.2015-019","article-title":"Paneth cell \u03b1-defensins and enteric microbiota in health and disease","volume":"35","author":"Nakamura","year":"2016","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Toropov, V., Demyanova, E., Shalaeva, O., Stikin, S., and Vakhitov, T. (2020). Whole-genome sequencing of Lactobacillus helveticus D75 and D76 confirms safety and probiotic potential. Microorganisms, 8.","DOI":"10.20944\/preprints201912.0354.v1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/09168451.2014.972325","article-title":"Adhesion properties of Lactobacillus rhamnosus mucus-binding factor to mucin and extracellular matrix proteins","volume":"79","author":"Nishiyama","year":"2015","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1099\/mic.0.073551-0","article-title":"Role of Lactobacillus reuteri cell and mucus-binding protein A (CmbA) in adhesion to intestinal epithelial cells and mucus in vitro","volume":"160","author":"Jensen","year":"2014","journal-title":"Microbiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/1875044301205010055","article-title":"Enhancement of epithelial barrier function by probiotics","volume":"5","author":"Madsen","year":"2012","journal-title":"J. Epithel. Biol. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/1348-0421.12719","article-title":"Lactobacillus helveticus SBT2171 upregulates the expression of \u03b2-defensin and ameliorates periodontal disease caused by Porphyromonas gingivalis","volume":"63","author":"Kobatake","year":"2019","journal-title":"Microbiol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pahumunto, N., Duangnumsawang, Y., and Teanpaisan, R. (2022). Effects of potential proviotics on the expression of cytokines and human \u03b2-defensin in human gingival epithelial cells and in vivo efficacy in a dog model. Arch. Oral Biol., 142.","DOI":"10.1016\/j.archoralbio.2022.105513"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Kim, K.H., Kim, H.J., Lee, J., and Myung, S.C. (2015). Expression of beta-defensin 131 promotes an innate immune response in human prostate epithelial cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144776"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1365-2249.2007.03587.x","article-title":"Probiotic lactobacilli and VSL#3 induce enterocyte \u03b2-defensin 2","volume":"151","author":"Schlee","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7428","DOI":"10.1128\/IAI.73.11.7428-7435.2005","article-title":"Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess","volume":"73","author":"Kielian","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1007\/s00018-005-5540-2","article-title":"Human \u03b2-defensins","volume":"63","author":"Pazgier","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1600-0765.2006.00964.x","article-title":"Human \u03b2 defensin-1 and -2 expression in the gingiva of patients with specific periodontal diseases","volume":"42","author":"Demirci","year":"2007","journal-title":"J. Periodont. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"036005","DOI":"10.1088\/1752-7163\/ab944d","article-title":"Effects of academic stress on the levels of oral volatile sulfur compounds, halitosis-related bacteria and stress biomarkers of healthy undergraduate students","volume":"14","author":"Nani","year":"2020","journal-title":"J. Breath Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ghosh, S.K., Feng, Z., Fujioka, H., Lux, R., McCormick, T.S., and Weinburg, A. (2018). Conceptual perspectives: Bacterial antimicrobial peptide induction as a novel strategy for symbiosis with the human host. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00302"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1007\/s10068-023-01451-6","article-title":"Preventive effect of Lacticaseibacillus paracasei LMT18-32 on Porphyromonas gingivalis induced periodontitis","volume":"33","author":"Choi","year":"2024","journal-title":"Food Sci. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Wu, J., Sum, Z., Fan, J., Liu, F., Zhao, W., Liu, W.H., Zhang, M., and Hung, W.L. (2023). Postbiotics derived from L. paracasei ET-22 inhibit the formation of S. mutans biofilms and bioactive substances: An analysis. Molecules, 28.","DOI":"10.3390\/molecules28031236"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7335","DOI":"10.1039\/D3FO02271D","article-title":"Lactobacillus paracasei ET-22 and derived postbiotics reduce halitosis and modulate oral microbiome dysregulation\u2014A randomized, double-blind placebo-controlled clinical trial","volume":"14","author":"Wuri","year":"2023","journal-title":"Food Func."},{"key":"ref_50","first-page":"1","article-title":"Lack of association between halitosis and the presence of Streptococcus mutans in saliva","volume":"10","author":"Ghapanchi","year":"2015","journal-title":"Br. J. Med. Med. Res."},{"key":"ref_51","first-page":"21266067","article-title":"The tongue biofilm metatransciptome identifies metabolic pathways associated with halitosis and its prevention","volume":"11","author":"Rosier","year":"2021","journal-title":"medRxiv"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/11\/2147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:20:16Z","timestamp":1760113216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/11\/2147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,25]]},"references-count":51,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["microorganisms12112147"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12112147","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,25]]}}}