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      Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial

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          Abstract

          Objectives

          The aim of this study was to evaluate the effects of Lactobacilli reuteri (Prodentis) alone and in combination with scaling and root planing (SRP) in a double blind, randomized, placebo-controlled clinical trial of volunteers with chronic periodontitis.

          Methods

          Thirty, otherwise systemically healthy, chronic periodontitis patients (19 males and 11 females, aged between 34 and 50 years) were included. The study period was 42 days. ‘Split-mouth’ design was used for the SRP, which was performed on day 0; two quadrants (either right or left) were treated with SRP whereas the remaining two quadrants were left untreated. The participants received a toothbrush, toothpaste, and brushing instructions. L. reuteri Prodentis lozenges (1×10 8 CFU DSM17938+1×10 8 CFU ATCC PTA 5289) or the corresponding placebo lozenges were taken twice daily from day 21 to day 42. Statistical analysis was done for comparisons of clinical parameters (Plaque Index (PI), Gingival Index (GI), Gingival Bleeding Index (GBI), probing pocket depth (PPD), clinical attachment level (CAL)) and microbiological levels of the pathogens Aggregibacter actinomycetemcomitans ( Aa), Porphyromonas gingivalis ( Pg), and Prevotella intermedia ( Pi). All p-values less than 0.05 were considered significant. Assessments were made on day 0 before SRP treatment, on day 21 before administration of the lozenges, and on day 42.

          Results

          At day 42, the PI, GI, and GBI were significantly reduced by all treatment modalities. When ranked, the amount of PI, GI and GBI reduction by the different treatments was SRP + Prodentis Prodentis SRP + placebo placebo; all differences were statistically significant. For PPD and CAL, the best result was obtained with the SRP+Prodentis treatment. PPD was reduced from 5.08±0.75 to 3.78±0.61 mm ( p<0.001) and CAL from 3.93±0.93 to 2.85±0.74 mm ( p<0.001). Prodentis, either alone or following SRP, reduced Aa, Pi, and Pg by 1 log 10 unit ( p<0.01). The SRP+placebo combination did not significantly affect the levels of the pathogens.

          Conclusion

          The present randomized controlled trial confirms the plaque inhibition, anti-inflammatory, and antimicrobial effects of L. reuteri Prodentis. L. reuteri Prodentis probiotic can be recommended during non-surgical therapy and the maintenance phase of periodontal treatment. Considering the beneficial effects of probiotics, this therapy could serve as a useful adjunct or alternative to periodontal treatment when SRP might be contraindicated. Further studies are required in this direction.

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          Most cited references31

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          Probiotic Lactobacillus reuteri biofilms produce antimicrobial and anti-inflammatory factors

          Background Commensal-derived probiotic bacteria inhibit enteric pathogens and regulate host immune responses in the gastrointestinal tract, but studies examining specific functions of beneficial microbes in the context of biofilms have been limited in scope. Results Lactobacillus reuteri formed biofilms that retained functions potentially advantageous to the host including modulation of cytokine output and the production of the antimicrobial agent, reuterin. Immunomodulatory activities of biofilms were demonstrated by the abilities of specific L. reuteri strains to suppress human TNF production by LPS-activated monocytoid cells. Quantification of the antimicrobial glycerol derivative, reuterin, was assessed in order to document the antipathogenic potential of probiotic biofilms. L. reuteri biofilms differed in the quantities of reuterin secreted in this physiological state. Conclusion L. reuteri biofilms secreted factors that confer specific health benefits such as immunomodulation and pathogen inhibition. Future probiotic selection strategies should consider a strain's ability to perform beneficial functions as a biofilm.
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            The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups.

            Reuterin is an antimicrobial compound produced by Lactobacillus reuteri, and has been proposed to mediate, in part, the probiotic health benefits ascribed to this micro-organism. Despite 20 years of investigation, the mechanism of action by which reuterin exerts its antimicrobial effects has remained elusive. Here we provide evidence that reuterin induces oxidative stress in cells, most likely by modifying thiol groups in proteins and small molecules. Escherichia coli cells subjected to sublethal levels of reuterin expressed a set of genes that overlapped with the set of genes composing the OxyR regulon, which senses and responds to various forms of oxidative stress. E. coli cells mutated for oxyR were more sensitive to reuterin compared with wild-type cells, further supporting a role for reuterin in exerting oxidative stress. The addition of cysteine to E. coli or Clostridium difficile growth media prior to exposure to reuterin suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly, interaction with E. coli stimulated reuterin production or secretion by L. reuteri, indicating that contact with other microbes in the gut increases reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol groups, which indicates that reuterin negatively affects a large number of cellular targets.
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              Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid.

              To investigate the effect of a chewing gum containing probiotic bacteria on gingival inflammation and the levels of selected inflammatory mediators in gingival crevicular fluid (GCF). Forty-two healthy adults with moderate levels of gingival inflammation entered a double-blind placebo-controlled study design. The subjects were randomly assigned to one of three parallel arms: Group A/P was given one active and one placebo gum daily, Group A/A received two active chewing gums, and Group P/P two placebo gums. The chewing gums contained two strains of Lactobacillus reuteri: ATCC 55730 and ATCC PTA 5289 (1 x 10(8) CFU/gum, respectively). The subjects were instructed to chew the gums for 10 min over the course of 2 weeks. Bleeding on probing (BOP) and GCF sampling were conducted at baseline and after 1, 2 and 4 weeks. The levels of IL-1beta, TNF-alpha, IL-6, IL-8 and IL-10 were determined using luminex technology and multiplex immunoassay kits. BOP improved and GCF volume decreased in all groups during the chewing period, but the results were statistically significant (p<0.05) only in Groups A/P and A/A. The levels of TNF-alpha and IL-8 decreased significantly (p<0.05) in Group A/A compared with baseline after 1 and 2 weeks, respectively. A non-significant decreasing tendency was also observed concerning IL-1beta during the chewing period. The levels of IL-6 and IL-10 were unaffected in all groups after 1 and 2 weeks. The reduction of pro-inflammatory cytokines in GCF may be proof of principle for the probiotic approach combating inflammation in the oral cavity.
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                Author and article information

                Journal
                J Oral Microbiol
                JOM
                Journal of Oral Microbiology
                CoAction Publishing
                2000-2297
                02 November 2010
                2010
                : 2
                : 10.3402/jom.v2i0.5344
                Affiliations
                [1 ]Department of Periodontics, Sri Hasanamba Dental College & Hospital, Hassan, Karnataka, India
                [2 ]Department of Periodontics, College of Dental Sciences, Davangere, Karnataka, India
                [3 ]Department of Microbiology and Immunology, Marata Mandals Dental College and Research Centre, Belgaum, Karnataka, India
                Author notes
                [* ] K.L. Vandana, Department of Periodontics, College of Dental Sciences, Davangere 577 004, Karnataka, India. Email: vanrajs@ 123456gmail.com
                Article
                JOM-2-5344
                10.3402/jom.v2i0.5344
                3084569
                21523225
                b86295d2-2575-44af-9058-508581ffd5bc
                © 2010 M.R. Vivekananda et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 June 2010
                : 05 October 2010
                : 05 October 2010
                Categories
                Original Article

                Microbiology & Virology
                gingivitis,anti-inflammatory,chronic generalized periodontitis,plaque,antimicrobial,dsm 17938,scaling and root planning,atcc pta 5289

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