New strategies for the control of periodontitis

• Grant number: 15/18273-9
• Support Opportunities: Research Projects - Thematic Grants
• Duration: April 01, 2016 - December 31, 2022
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Marcia Pinto Alves Mayer
• Grantee: Marcia Pinto Alves Mayer
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Maria Regina Lorenzetti Simionato ; Raquel Mantuaneli Scarel Caminaga
• Associated researchers: Bruno Bueno Silva ; Carlos Ferreira dos Santos ; Caroline Marcantonio Ferreira ; Cláudio Mendes Pannuti ; Cristina Cunha Villar ; Ellen Sayuri Ando Suguimoto ; Fernando Neves Nogueira ; Giuseppe Alexandre Romito ; Katia Sivieri ; Luciana Saraiva ; Magda Feres Figueiredo ; Marcelo de Faveri ; Marinella Holzhausen Caldeira ; Niels Olsen Saraiva Câmara ; Pedro Luiz Rosalen ; Priscila Larcher Longo
• Associated scholarship(s): 21/13846-1 - Effect of probiotic Lactobacillus acidophilus LA5 on protein expression related to intestinal barrier integrity in a model of periodontitis induced by Aggregatibacter actinomycetemcomitans, BP.IC; 19/16164-9 - Determination of adhesion efficiency of A. actinomycetemcomitans, S. gordonii and S. oralis on the acquired pellicle formed with saliva from patients with localized aggressive periodontitis and controls with family related and not related, BP.IC; 19/05256-0 - Effect of probiotics on the genus Lactobacillus on oral colonization and spread of P. gingivalis systemic in experimental periodontitis model in mice, BP.IC; + associated scholarships 18/02318-1 - Effect of probiotic lactobacilli on the modulation of inflammassome and alveolar bone loss promoted by experimental periodontitis in healthy mice, BP.MS; 17/22345-0 - Effect of Bifidobacterium probiotics on the modulation of immune response and alveolar bone loss in an experimental periodontitis model on normoglycemic and diabetic mice, BP.MS; 17/16377-7 - EVALUATION OF THE EFFECT OF PROBIOTIC BACTERIA ON THE IMUNE RESPONSE TO A.ACTINOMYCETEMCOMITANS: A STUDY IN GINGIVAL EPITHELIAL CELLS AND IN EXPERIMENTAL MODEL OF INFECTION IN VIVO., BP.DR; 17/10829-3 - Immunomodulatory effect of probiotic bacteria: analysis in peripheral monocytes and dendritic cells., BP.PD; 16/14687-6 - Evaluation of immunomodulatory potential of probiotics in periodontal disease, BP.DR; 16/13156-7 - Direct and immunomodulatory effects of probiotic bacteria on periodontal pathogens, BP.PD; 16/13159-6 - Supra and subgingival microbiota diversity analysis and protein profile of saliva and enamel film of individuals with chronic periodontitis and microbial succession, BP.PD - associated scholarships

Abstract

We aim to establish the bases for the development of new strategies for the control of periodontitis. Our hypothesis is that the balance between the oral microbiota-immune response, lost in periodontitis, could be obtained by favoring the colonization of the oral cavity with beneficial bacterial species and by modulating the immune response. The first project aims to test if saliva differs according to the periodontal condition, identifying potential biomarkers in localized aggressive and chronic periodontitis and their controls. Microbiome will be determined by 16SrRNA sequencing in oral and fecal samples. Proteome of saliva (total and parotid) and of the acquired pellicle will be determined. The expanded exome will be investigated. We hope to demonstrate that differences in saliva composition, due to genomic variations, are correlated with differences in oral microbiome associated with each periodontal condition. The second project aims to correlate functional aspects of saliva with its composition. Differences in affinity of microbial groups to the pellicle will be determined by biofilm formation assays, with inocula formed by biofilm samples and isolated species. Depending on the initial data, recombinant proteins or synthetic peptides can be used in further functional analysis. The third project aims to test if probiotics present antagonism against the oral pathogenic microbiota. Lactobacillus and Bifidobacterium species will be evaluated regarding their effect on P. gingivalis and A. actinomycetemcomitans. The ability of probiotics to inhibit growth and/or virulence factors expression and to compete for adhesion sites in gingival epithelial cells will be determined. The effect of probiotics on manipulating the oral and gut microbiota will be evaluated by using the Shime model added with the mouth compartment. The effect of probiotics on the composition of dental biofilm and their cariogenic potential will be determined in situ. We hope to select the probiotic strains able to manipulate the oral microbiota, by antagonizing with periodontopathogens. The fourth project aims to determinate the ability of probiotics to modulate the immune response. Co-culture assays with probiotics, periodontopathogens and epithelial cells (OBA-09 and primary), human monocytes (THP-1 and peripherical) and murine (wild and KO in IL-1r, IL-18, TLR-2 and TLR-4) BMCs differentiated in macrophages, and dendritic cells will be used to test for cytokines production, gene expression, signaling pathways and functionality on lymphocytes subtypes differentiation. Probiotics will be tested in periodontitis animal models with P. gingivalis and A. actinomycetemcomitans in normal and diabetic mice. We hope to select the probiotic strains able to colonize the oral cavity and to induce an immune response favoring a health-associated microbiota, in balance with the host. Aiming to test if probiotics can be used as adjuvant to the periodontal treatment, the fifth project will evaluate the effect of probiotics on the oral and gut microbiota in humans, and on clinical parameters and cytokines production. Probiotics-containing lozenges will be used in periodontally treated patients for 180 days. We hope to demonstrate that probiotics are able to reestablish the balance in periodontitis patients during maintenance treatment phase, and thus suggest their use as a therapeutic strategy in the control of periodontitis, and possibly of other associated conditions. These data will contribute to the establishment of strategies able to interfere with dysbiosis and host immune response to the resident microbiota, favoring health. (AU)

Scientific publications

(16)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ISHIKAWA, KARIN H.; BUENO, MANUELA R.; KAWAMOTO, DIONE; SIMIONATO, MARIA R. L.; MAYER, MARCIA P. A.. actobacilli postbiotics reduce biofilm formation and alter transcription of virulence genes of Aggregatibacter actinomycetemcomitan. Molecular Oral Microbiology, v. 36, n. 1, JAN 2021. (15/18273-9, 17/16377-7, 16/13156-7)

ANDO-SUGUIMOTO, ELLEN S.; BENAKANAKERE, MANJUNATHA R.; MAYER, MARCIA P. A.; KINANE, DENIS F.. Distinct Signaling Pathways Between Human Macrophages and Primary Gingival Epithelial Cells by Aggregatibacter actinomycetemcomitans. PATHOGENS, v. 9, n. 4, APR 2020. (12/05887-0, 15/18273-9)

SHIMABUKURO, NATALI; CATARUCI, AMALIA C. DE S.; ISHIKAWA, KARIN H.; OLIVEIRA, BRUNA E. DE; KAWAMOTO, DIONE; ANDO-SUGUIMOTO, ELLEN S.; ALBUQUERQUE-SOUZA, EMMANUEL; NICOLI, JACQUES R.; FERREIRA, CAROLINE M.; DE LIMA, JEAN; et al. Bifidobacterium Strains Present Distinct Effects on the Control of Alveolar Bone Loss in a Periodontitis Experimental Model. FRONTIERS IN PHARMACOLOGY, v. 12, SEP 24 2021. (17/22345-0, 15/18273-9, 16/13156-7, 18/25171-6, 16/14687-6, 17/16377-7, 16/13159-6)

ALBUQUERQUE-SOUZA, EMMANUEL; ISHIKAWA, KARIN HITOMI; AMADO, PAMELA PENAS; NICOLI, JACQUES ROBERT; HOLZHAUSEN, MARINELLA; MAYER, MARCIA P. A.. Probiotics improve re-epithelialization of scratches infected by Porphyromonas gingivalis through up-regulating CXCL8-CXCR1/CXCR2 axis. Anaerobe, v. 72, DEC 2021. (16/13156-7, 15/18273-9, 16/14687-6)

AMADO, PAMELA PONTES PENAS; KAWAMOTO, DIONE; ALBUQUERQUE-SOUZA, EMMANUEL; FRANCO, DIEGO CASTILLO; SARAIVA, LUCIANA; CASARIN, RENATO CORREA VIANA; HORLIANA, ANNA CAROLINA RATTO TEMPESTINI; MAYER, MARCIA PINTO ALVES. Oral and Fecal Microbiome in Molar-Incisor Pattern Periodontitis. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, OCT 8 2020. (15/00259-0, 16/14687-6, 16/13159-6, 15/18273-9)

ISHIKAWA, KARIN H.; BUENO, MANUELA R.; KAWAMOTO, DIONE; SIMIONATO, MARIA R. L.; MAYER, MARCIA P. A.. Lactobacilli postbiotics reduce biofilm formation and alter transcription of virulence genes of Aggregatibacter actinomycetemcomitans. Molecular Oral Microbiology, v. 36, n. 1, p. 11-pg., 2021-01-17. (15/18273-9, 17/16377-7, 16/13156-7)

VALE, GLAUBER CAMPOS; MOTA, BRENDA IZABELA SANTANA; ANDO-SUGUIMOTO, ELLEN SAYURI; MAYER, MARCIA PINTO ALVES. Lactobacilli Probiotics Modulate Antibacterial Response Gene Transcription of Dendritic Cells Challenged with LPS. PROBIOTICS AND ANTIMICROBIAL PROTEINS, v. N/A, p. 15-pg., 2023-01-25. (15/18273-9, 17/10829-3)

KAWAMOTO, DIONE; LUCAS AMADO, PAMELA PONTES; ALBUQUERQUE-SOUZA, EMMANUEL; BUENO, MANUELA ROCHA; VALE, GLAUBER CAMPOS; SARAIVA, LUCIANA; ALVES MAYER, MARCIA PINTO. Chemokines and cytokines profile in whole saliva of patients with periodontitis. CYTOKINE, v. 135, p. 9-pg., 2020-11-01. (16/13159-6, 17/16377-7, 15/00259-0, 17/10829-3, 15/18273-9)

MATSUBARA, VICTOR H.; ISHIKAWA, KARIN H.; ANDO-SUGUIMOTO, ELLEN S.; BUENO-SILVA, BRUNO; NAKAMAE, ATLAS E. M.; MAYER, MARCIA P. A.. Probiotic Bacteria Alter Pattern-Recognition Receptor Expression and Cytokine Profile in a Human Macrophage Model Challenged with Candida albicans and Lipopolysaccharide. FRONTIERS IN MICROBIOLOGY, v. 8, NOV 29 2017. (15/18273-9)

ISHIKAWA, KARIN HITOMI; MITA, DANIELA; KAWAMOTO, DIONE; NICOLI, JACQUES ROBERT; ALBUQUERQUE-SOUZA, EMMANUEL; LORENZETTI SIMIONATO, MARIA REGINA; ALVES MAYER, MARCIA PINTO. Probiotics alter biofilm formation and the transcription ofPorphyromonas gingivalisvirulence-associated genes. JOURNAL OF ORAL MICROBIOLOGY, v. 12, n. 1, JAN 1 2020. (16/13156-7, 15/18273-9, 16/14687-6, 16/13159-6)

BUENO, MANUELA R.; ISHIKAWA, KARIN H.; ALMEIDA-SANTOS, GISLANE; ANDO-SUGUIMOTO, ELLEN S.; SHIMABUKURO, NATALI; KAWAMOTO, DIONE; MAYER, MARCIA P. A.. Lactobacilli Attenuate the Effect of Aggregatibacter actinomycetemcomitans Infection in Gingival Epithelial Cells. FRONTIERS IN MICROBIOLOGY, v. 13, p. 11-pg., 2022-05-04. (16/13159-6, 17/16377-7, 16/13156-7, 16/14687-6, 15/18273-9, 17/22345-0)

VALE, GLAUBER CAMPOS; SANTANA MOTA, BRENDA IZABELA; ANDO-SUGUIMOTO, ELLEN SAYURI; ALVES MAYER, MARCIA PINTO. Effect of Probiotics Lactobacillus acidophilus and Lacticaseibacillus rhamnosus on Antibacterial Response Gene Transcription of Human Peripheral Monocytes. PROBIOTICS AND ANTIMICROBIAL PROTEINS, AUG 2021. (15/18273-9, 17/10829-3)

ALBUQUERQUE-SOUZA, EMMANUEL; BALZARINI, DANILO; ANDO-SUGUIMOTO, ELLEN S.; ISHIKAWA, KARIN H.; SIMIONATO, MARIA R. L.; HOLZHAUSEN, MARINELLA; MAYER, MARCIA P. A.. Probiotics alter the immune response of gingival epithelial cells challenged by Porphyromonas gingivalis. JOURNAL OF PERIODONTAL RESEARCH, v. 54, n. 2, p. 115-127, APR 2019. (15/18273-9, 16/14687-6)

VALE, GLAUBER CAMPOS; ALVES MAYER, MARCIA PINTO. Effect of probiotic Lactobacillus rhamnosus by-products on gingival epithelial cells challenged with Porphyromonas gingivalis. ARCHIVES OF ORAL BIOLOGY, v. 128, AUG 2021. (17/10829-3, 15/18273-9)

SALGACO, MATEUS KAWATA; DE OLIVEIRA, FELLIPE LOPES; SARTORATTO, ADILSON; MESA, VICTORIA; MAYER, MARCIA PINTO ALVES; SIVIERI, KATIA. Impact of Lactobacillus acidophilus-La5 on Composition and Metabolism of the Intestinal Microbiota of Type 2 Diabetics (T2D) and Healthy Individuals Using a Microbiome Model. FERMENTATION-BASEL, v. 9, n. 8, p. 17-pg., 2023-08-01. (19/17794-6, 15/18273-9)

KAWAMOTO, DIONE; BORGES, RODRIGO; RIBEIRO, RODOLFO ALVARENGA; DE SOUZA, ROBSON FRANCISO; AMADO, PAMELA PONTES PENAS; SARAIVA, LUCIANA; HORLIANA, ANA CAROLINA RATTO TEMPESTINI; FAVERI, MARCELO; MAYER, MARCIA PINTO ALVES. Oral Dysbiosis in Severe Forms of Periodontitis Is Associated With Gut Dysbiosis and Correlated With Salivary Inflammatory Mediators: A Preliminary Study. FRONTIERS IN ORAL HEALTH, v. 2, p. 15-pg., 2021-10-11. (16/13159-6, 15/18273-9)