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https://www.arca.fiocruz.br/handle/icict/53983
METHOTREXATE PROMOTES RECOVERY OF ARTHRITIS-INDUCED ALVEOLAR BONE LOSS AND MODIFIES THE COMPOSITION OF THE ORAL-GUT MICROBIOTA
Antirheumatic agents
Gut microbiome
Methotrexate
Microbiota
Rheumatoid arthritis
Author
Arruda, José Alcides Almeida de
Corrêa, Jôice Dias
Singh, Youvika
Oliveira, Sicília Rezende
Machado, Caio Cavalcante
Schneider, Ayda Henriques
Medeiros, Julliane Dutra
Fernandes, Gabriel da Rocha
Macari, Soraia
Barrioni, Breno Rocha
Santos, Mariana de Souza
Duffles, Letícia Fernanda
Nakaya, Helder Takashi Imoto
Fukada, Sandra Yasuyo
Graves, Dana T
Cunha, Fernando Queiroz
Silva, Tarcília Aparecida
Corrêa, Jôice Dias
Singh, Youvika
Oliveira, Sicília Rezende
Machado, Caio Cavalcante
Schneider, Ayda Henriques
Medeiros, Julliane Dutra
Fernandes, Gabriel da Rocha
Macari, Soraia
Barrioni, Breno Rocha
Santos, Mariana de Souza
Duffles, Letícia Fernanda
Nakaya, Helder Takashi Imoto
Fukada, Sandra Yasuyo
Graves, Dana T
Cunha, Fernando Queiroz
Silva, Tarcília Aparecida
Affilliation
Department of Oral Surgery. Pathology and Clinical Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Dentistry. Pontifical Catholic University. Belo Horizonte, MG, Brazil.
Department of Clinical and Toxicological Analysis. Faculty of Pharmaceutical Sciences. University of São Paulo. São Paulo, SP, Brazil.
Department of Oral Surgery. Pathology and Clinical Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Pharmacology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Pharmacology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil.
Faculty of Biological and Agricultural Sciences. Mato Grosso State University. Alta Floresta, MT, Brazil.
René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Department of Restorative Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Metallurgical and Materials Engineering, Faculty of Engineering, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Department of Restorative Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of BioMolecular Sciences. School of Pharmacological Science. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Clinical and Toxicological Analysis. Faculty of Pharmaceutical Sciences. University of São Paulo. São Paulo, SP, Brazil.
Department of BioMolecular Sciences. School of Pharmacological Science. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Periodontics. School of Dental Medicine. University of Pennsylvania. Philadelphia, PA, United States.
Department of Pharmacology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Oral Surgery. Pathology and Clinical Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Dentistry. Pontifical Catholic University. Belo Horizonte, MG, Brazil.
Department of Clinical and Toxicological Analysis. Faculty of Pharmaceutical Sciences. University of São Paulo. São Paulo, SP, Brazil.
Department of Oral Surgery. Pathology and Clinical Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Pharmacology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Pharmacology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil.
Faculty of Biological and Agricultural Sciences. Mato Grosso State University. Alta Floresta, MT, Brazil.
René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Department of Restorative Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Metallurgical and Materials Engineering, Faculty of Engineering, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Department of Restorative Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of BioMolecular Sciences. School of Pharmacological Science. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Clinical and Toxicological Analysis. Faculty of Pharmaceutical Sciences. University of São Paulo. São Paulo, SP, Brazil.
Department of BioMolecular Sciences. School of Pharmacological Science. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Periodontics. School of Dental Medicine. University of Pennsylvania. Philadelphia, PA, United States.
Department of Pharmacology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil.
Department of Oral Surgery. Pathology and Clinical Dentistry. School of Dentistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Abstract
Objectives: The impact of rheumatoid arthritis (RA) on the shaping of the oral and gut microbiome raises the question of whether and how RA treatment modifies microbial communities. We examined changes in the oral and gut microbiota in a mouse model of antigen-induced arthritis (AIA) treated or not with methotrexate (MTX).
Methods: Maxillae and stools were evaluated by the MiSeq platform of the V4 region of the 16S rRNA gene. Alveolar bone parameters were analysed by micro-computed tomography. Moreover, arthritis-induced changes in hyperalgesia and oedema were assessed, along with the impact on periodontal bone health.
Results: Microbial communities in MTX-treated AIA mice revealed distinct clusters compared to the control and AIA groups. Overall, MTX impacted the richness and variability of microorganisms in the oral-gut axis microbiome at the phylum level. Regarding the oral microbiome, while in the control group the most dominant phylum was Firmicutes, in the AIA group there was a shift towards the predominance of Campilobacteriota and Bacteroidetes associated with the disease. MTX treatment led to greater dominance of the health-associated phylum Proteobacteria. In the gut microbiome, AIA induction resulted in increased abundance of the Verrucomicrobiota phylum, and MTX treatment restored its levels compared to control. Importantly, the MTX-treated AIA animals had significantly less periodontal bone loss, as well as decreased hyperalgesia and joint oedema compared to the AIA animals.
Conclusion: Data suggest the benefit of MTX treatment in protecting alveolar bone, in addition to providing new insights on the drug-microbiome interaction in the course of RA.
Keywords
Alveolar bone lossAntirheumatic agents
Gut microbiome
Methotrexate
Microbiota
Rheumatoid arthritis
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