Methotrexate and Non-Surgical Periodontal Treatment Change the Oral–Gut Microbiota in Rheumatoid Arthritis: A Prospective Cohort Study

Oliveira, Sicília Rezende; de Arruda, José Alcides Almeida; Corrêa, Jôice Dias; Carvalho, Valessa Florindo; Medeiros, Julliane Dutra; Schneider, Ayda Henriques; Machado, Caio Cavalcante; Duffles, Letícia Fernanda; Fernandes, Gabriel da Rocha; Calderaro, Débora Cerqueira; Júnior, Mario Taba; Abreu, Lucas Guimarães; Fukada, Sandra Yasuyo; Oliveira, Renê Donizeti Ribeiro; Louzada-Júnior, Paulo; Cunha, Fernando Queiroz; Silva, Tarcília Aparecida

doi:10.3390/microorganisms12010068

Cited by 2 publications

(1 citation statement)

References 57 publications

(94 reference statements)

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“…It has been documented that RA can originate from mucosal locations, including the intestine and oral cavity [38]. Several molecular studies have shown that dysbiosis in patients with RA is characterized by the loss of Bacteroidetes with an overgrowth of Prevotella copri (P. copri) in the intestine, also in patients treated with methotrexate [39,40]. This phenomenon is especially common in patients carrying the "shared epitope" [41].…”

Section: Influence Of the Microbiome On Autoimmunitymentioning

confidence: 99%

Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies

Pérez-Pérez,

Nieto-Torres,

Bollain-y-Goytia

et al. 2024

IJMS

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The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100–200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case–control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal–Wallis test and Mann–Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.

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Section: Influence Of the Microbiome On Autoimmunitymentioning

confidence: 99%

Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies

Pérez-Pérez,

Nieto-Torres,

Bollain-y-Goytia

et al. 2024

IJMS

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Exploring the Role of the Microbiome in Rheumatoid Arthritis—A Critical Review

Ermencheva,

Kotov,

Shumnalieva

et al. 2024

Microorganisms

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Rheumatoid arthritis (RA) is a chronic, autoimmune rheumatic disease characterized by synovial joint inflammation with subsequent destruction as well as systemic manifestation, leading to impaired mobility and impaired quality of life. The etiopathogenesis of RA is still unknown, with genetic, epigenetic and environmental factors (incl. tobacco smoking) contributing to disease susceptibility. The link between genetic factors like “shared epitope alleles” and the development of RA is well known. However, why only some carriers have a break in self-tolerance and develop autoimmunity still needs to be clarified. The presence of autoantibodies in patients’ serum months to years prior to the onset of clinical manifestations of RA has moved the focus to possible epigenetic factors, including environmental triggers that could contribute to the initiation and perpetuation of the inflammatory reaction in RA. Over the past several years, the role of microorganisms at mucosal sites (i.e., microbiome) has emerged as an essential mediator of inflammation in RA. An increasing number of studies have revealed the microbial role in the immunopathogenesis of autoimmune rheumatic diseases. Interaction between the host immune system and microbiota initiates loss of immunological tolerance and autoimmunity. The alteration in microbiome composition, the so-called dysbiosis, is associated with an increasing number of diseases. Immune dysfunction caused by dysbiosis triggers and sustains chronic inflammation. This review aims to provide a critical summary of the literature findings related to the hypothesis of a reciprocal relation between the microbiome and the immune system. Available data from studies reveal the pivotal role of the microbiome in RA pathogenesis.

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Methotrexate and Non-Surgical Periodontal Treatment Change the Oral–Gut Microbiota in Rheumatoid Arthritis: A Prospective Cohort Study

Cited by 2 publications

References 57 publications

Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies

Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies

Exploring the Role of the Microbiome in Rheumatoid Arthritis—A Critical Review

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