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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.

Grant number: 17/16377-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2017
Effective date (End): March 31, 2022
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Marcia Pinto Alves Mayer
Grantee:Manuela Rocha Bueno
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/18273-9 - New strategies for the control of periodontitis, AP.TEM

Abstract

The project aims to test the hypothesis that probiotic microorganisms or their products are able to control periodontitis induced by Aggregatibacter actinomycetemcomitans (Aa) by regulating the immune response to this pathogen. Initial results indicate that probiotics L.rhamnosus Lr32 and HN001 and L. acidophilus NCFM and La5 interfere with fimbria mediated biofilm formation of A. actinomycetemcomitans. In addition, probiotic lactobacilli and bifidobacteria are capable of altering the cytokine profile produced by epithelial cells and macrophages after challenge with P. gingivalis and E. coli LPS, and to reduce the adhesion and invasion of P. gingivalis in gingival epithelial cells, indicating its potential in modulating inflammation. Aggressive periodontitis is associated with a complex microbiota, including A. actinomycetemcomitans. The present proposal aims to determine the ability of probiotic strains to modulate the immune response against Aa in in vitro and animal models. Gingival epithelial cells (OBA-9 strain) will be used and the effect of probiotics on the pathogen's adhesion and invasion capacity, cytokine profile, expression of genes associated with the inflammatory process and activation of signaling pathways will be evaluated. Probiotic strains will be tested in an animal model inoculated with A. actinomycetemcomitans in normal and diabetic rats. With the strategies employed, we hope to select probiotic strain (s) capable of interfering with Aa colonization and induce a response capable of altering the oral and gut microbiota favoring the health-associated microbiota in equilibrium with the host.

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Scientific publications (6)
(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.. Lactobacilli postbiotics reduce biofilm formation and alter transcription of virulence genes of Aggregatibacter actinomycetemcomitans. Molecular Oral Microbiology, v. 36, n. 1, p. 11-pg., . (15/18273-9, 17/16377-7, 16/13156-7)
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, . (17/22345-0, 15/18273-9, 16/13156-7, 18/25171-6, 16/14687-6, 17/16377-7, 16/13159-6)
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, . (15/18273-9, 17/16377-7, 16/13156-7)
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., . (16/13159-6, 17/16377-7, 15/00259-0, 17/10829-3, 15/18273-9)
BUENO, MANUELA ROCHA; DUDU-SILVA, GUSTAVO; MACEDO, TATIANE TIEMI; GOMES, ALINE PAIM DE ABREU PAULO; BRAGA, ARTHUR RODRIGUES OLIVEIRA; AGUIAR SILVA, LUCAS DAYLOR; BUENO-SILVA, BRUNO. Lactobacillus acidophilus impairs the establishment of pathogens in a subgingival multispecies biofilm. FRONTIERS IN DENTAL MEDICINE, v. 4, p. 7-pg., . (17/16377-7)
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., . (16/13159-6, 17/16377-7, 16/13156-7, 16/14687-6, 15/18273-9, 17/22345-0)

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