Topical treatment with probiotic Lactobacillus brevis CD2 inhibits experimental periodontal inflammation and bone loss.
OBJECTIVE
An increasing body of evidence suggests that the use of probiotic bacteria is a promising intervention approach for the treatment of inflammatory diseases with a polymicrobial etiology. The objective of this study was to determine whether Lactobacillus brevis CD2 could inhibit periodontal inflammation and bone loss in experimental periodontitis.


METHODS
Periodontitis was induced by placing a silk ligature around the second maxillary molar of mice treated with L. brevis CD2 (8 × 10(5)  CFU in 1 mm(2) lyopatch) or placebo, which were placed between the gingiva and the buccal mucosa near the ligated teeth. The mice were killed after 5 d and bone loss was measured morphometrically, gingival expression of proinflammatory cytokines was determined by quantitative real-time polymerase chain reaction, and CFU counts of periodontitis-associated bacteria were determined after aerobic and anaerobic culture. To determine the role of arginine deiminase released by L. brevis CD2, soluble extracts with or without formamidine (arginine deiminase inhibitor) were tested in in vitro cellular activation assays.


RESULTS
Mice topically treated with L. brevis CD2 displayed significantly decreased bone loss and lower expression of tumor necrosis factor, and interleukin-1β, -6 and -17A as compared to placebo-treated mice. Moreover, L. brevis CD2-treated mice displayed lower counts of anaerobic bacteria but higher counts of aerobic bacteria than placebo-treated mice. In in vitro assays, the anti-inflammatory effects of soluble L. brevis CD2 extracts were heavily dependent on the presence of functional arginine deiminase, an enzyme that can inhibit nitric oxide synthesis.


CONCLUSIONS
These data provide proof-of-concept that the probiotic L. brevis CD2 can inhibit periodontitis through modulatory effects on the host response and the periodontal microbiota.
Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
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Maekawa
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Hajishengallis
D000287:Administration, Topical; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001420:Bacteria, Aerobic / Q000187:drug effects; D001421:Bacteria, Anaerobic / Q000187:drug effects; D058491:Bacterial Load; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D004926:Escherichia coli; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020381:Interleukin-17 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D052196:Levilactobacillus brevis / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000032:analysis; D010518:Periodontitis / Q000382:microbiology / Q000517:prevention & control*; D010919:Placebos; D016966:Porphyromonas gingivalis; D019936:Probiotics / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000578:Amidines; D016207:Cytokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C077922:formamidine; D006867:Hydrolases; C019723:arginine deiminase
Lactobacillus brevis CD2; arginine deiminase; inflammation; periodontitis; probiotics