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Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dysbiotic oral biofilms produce virulence factors, such as lipopolysaccharide (LPS), triggering and sustaining chronic inflammation in periodontal tissues. Modulation of the bioactivity of these products offers a potential novel, adjunctive approach beyond conventional periodontal therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pooled saliva and subgingival biofilm samples from 324 healthy, gingivitis, and periodontitis participants were assessed for endotoxin activity using the recombinant Factor C (rFC) assay. Functional immune-stimulation was evaluated in THP-1 and THP-1 Dual cell models through NF-\u03baB and IRF pathways activation assessment and cytokine profiling. The modulatory effects of antimicrobial peptide LL-37 and the LPS-binding compound Polymyxin B on saliva and subgingival biofilm inflammatory potential were assessed in the same models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Recombinant Factor C assays demonstrated marked reductions in endotoxin activity of saliva and subgingival biofilms treated with LL-37 and Polymyxin B (&amp;gt;90% reduction). Both NF-\u03baB and IRF signaling were broadly attenuated following modulation, with polymyxin B exerting greater suppression of NF-\u03baB activity, while LL-37 showed stronger inhibition of IRF, particularly in salivary samples. Pro-inflammatory cytokines secretion by THP-1 cells (IL-1\u03b2, IL-6, IL-8, and TNF-\u03b1) challenged with bio-modulated samples decreased by 40\u201375% compared to untreated samples. Interestingly, anti-inflammatory cytokines such as TGF-\u03b2 and IL-10 remained largely unchanged, suggesting selective suppression of the cytokine cascade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Modulating LPS-associated virulence activity substantially reduces the inflammatory potential of saliva and subgingival plaque. LL-37 and Polymyxin B illustrate complementary strategies for LPS modulations and highlight the feasibility of their use as adjunctive approaches for the prevention and treatment of periodontal diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1728315","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T12:26:11Z","timestamp":1769775971000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Modulation of LPS-associated virulence activity for reduction of periodontal inflammatory burden"],"prefix":"10.3389","volume":"17","author":[{"given":"Anbo","family":"Dong","sequence":"first","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Lehto","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics, Folkh\u00e4lsan Research Center","place":["Helsinki, Finland"]},{"name":"Department of Nephrology, University of Helsinki and Helsinki University Hospital","place":["Helsinki, Finland"]},{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki","place":["Helsinki, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Putaala","sequence":"additional","affiliation":[{"name":"Department of Neurology, Helsinki University Hospital and University of Helsinki","place":["Helsinki, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Paju","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, University of Helsinki","place":["Helsinki, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirkko","family":"Pussinen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, University of Helsinki","place":["Helsinki, Finland"]},{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland","place":["Kuopio, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetislav","family":"Zaric","sequence":"additional","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4474","DOI":"10.1128\/iai.01924-05","article-title":"Hemin-dependent modulation of the lipid A structure of Porphyromonas gingivalis lipopolysaccharide","volume":"74","author":"Al-Qutub","year":"2006","journal-title":"Infect. 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