| Summary: | Probiotics, active microorganisms benefiting human health, currently serve as nutritional supplements and clinical treatments. Periodontitis, a chronic infectious oral disease caused by <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), activates the host immune response to release numerous proinflammatory cytokines. Here, we aimed to clarify <i>Leuconostoc mesenterica</i> (<i>L. mesenteroides</i>) LVBH107 probiotic effects based on the inhibition of <i>P. </i><i>gingivalis</i> activities while also evaluating the effectiveness of an in vitro <i>P. </i><i>gingivalis</i> lipopolysaccharide-stimulated RAW 264.7 cell-based inflammation mode. <i>L. mesenteroides</i> LVBH107 survived at acid, bile salts, lysozyme, and hydrogen peroxide conditions, auto-aggregated and co-aggregated with <i>P. gingivalis</i>, exhibited strong hydrophobicity and electrostatic action, and strongly adhered to gingival epithelial and HT-29 cells (thus exhibiting oral tissue adherence and colonization abilities). Moreover, <i>L. </i><i>mesenteroides</i> LVBH107 exhibited sensitivity to antibiotics erythromycin, doxycycline, minocycline, ampicillin, and others (thus indicating it lacked antibiotic resistance plasmids), effectively inhibited <i>P. </i><i>gingivalis</i> biofilm formation and inflammation (in vitro inflammation model), reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and inflammatory mediators (NO and PGE<sub>2</sub>), and decreased the expression levels of inflammation related genes. Thus, <i>L. </i><i>mesenterica</i> LVBH107 holds promise as a probiotic that can inhibit <i>P. </i><i>gingivalis</i> biofilm formation and exert anti-inflammatory activity to maintain oral health.
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