Microbiome & Chronic Diseases

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Disease ⇒ Rheumatoid Arthritis {40000107}

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Rheumatoid Arthritis
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Musculoskeletal, Rheumatology, Immunology
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- ACPA generation may be associated with larger populations of Prevotellaceae in both oral and intestinal microbiomes. In response to such altered microbial flora, certain predisposed individuals may develop auto-inflammatory disease, through mechanisms that may include the generation of cyclic citrullinated peptides or Th17 cell activation in the intestinal mucosa. (4)

References Notes

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Shared Reference Notes

  • [1.23
    - Porphyromonas gingivalis is a leading pathogen in chronic periodontitis, a disease process involving progressive destruction of the tissues that support the teeth. Recently, the organism has been reported to produce a unique bacterial enzyme, P. gingivalis peptidyl-arginine deiminase (PPAD), which has the ability to convert arginine residues in proteins to citrulline. Protein citrullination alters protein structure and function; hence, PPAD may be involved in deregulation of the host signalling network and immune evasion.
  • [1.24
    - Prevotella is a crucial genus in the onset of other chronic inflammatory disorders such as rheumatoid arthritis - Ther is a strong association between Prevotella copri and new-onset untreated rheumatoid arthritis and the higher abundance of Prevotella was associated with a reduction in several beneficial microbes, including Bacteroides.
  • [1.25
    - In a region in Eastern India endemic for lymphatic filariasis caused by filarial worms, not a single person with rheumatoid arthritis (RA) tested positive for circulating filarial antigens - Much higher proportion (40%) of people without RA tested positive for the nematode.
  • [1.26
    - Significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA.
  • [1.27
    - reduced abundance of Desulfovibrionaceae Bilophila, Akkermansia, and Veillonellaceae Dialister and increased levels of Lachnospiraceae Clostridium as most predictive of disease state. - increased Clostridiaceae Clostridium and Lachnospiraceae and reduced Erysipelotrichaceae were three of the eight identified in all RA models.
  • [1.28
    - Abundance of specific gut bacterial taxa and their genes enhances the clinical response to orthologs related to purine and methotrexate metabolism.
  • [1.29] [#Porphyromonas gingivalis
    - The presence of P. gingivalis in the GI microbiota has been linked with a milieu of inflammatory/autoimmune diseases associated with GI dysbiosis including RA and NAFLD
  • [1.30
    - Patients with RA showed an altered metabolic capacity for transporting zinc and copper. The study authors suggest that these alterations may significantly influence the perpetuations of the autoimmunity of RA. - Porphyromonas gingivalis (discussed within “Periodontal Microbiome and ACPA” section), Proteus mirabilis, Mycobacterium tuberculosis, and Mycoplasma spp are associated with an increased risk of RA development.
  • [1.31
    - Increased serum levels of the antibodies IgM rheumatoid factor (IgM-RF) and antibodies against #Citrullinated Proteins (ACPA) in healthy individuals imply an elevated risk of developing RA - The possible role of #Porphyromonas gingivalis in the immunopathogenesis of RA has been of particular interest due to its capacity to generate #Citrullinated Proteins.
  • [1.32
    - #Prevotella in saliva is at higher relative abundance compared to healthy controls.
  • - #Veillonella in saliva and tongue coating is at higher relative abundance compared to healthy controls.
  • [1.34
    - RA patients display increased levels of serum markers of gut permeability and damage and cellular gut-homing markers, both parameters (LPB, LPS, and I-FABP) positively correlating with disease severity. - Arthritic mice display increased gut permeability from early stages of disease, as well as bacterial translocation, inflammatory gut damage, increases in interferon γ (IFNγ)+ and decreases in IL-10+ intestinal-infiltrating leukocyte frequency, and reduced intestinal epithelial IL-10R expression. - Both arthritogenic bacteria and leukocytes are required to disrupt gut-barrier integrity. - Exposing intestinal organoids to IFNγ reduces IL-10R expression by epithelial cells and that mice lacking epithelial IL-10R display increased intestinal permeability and exacerbated arthritis. - Treatment of mice with AT-1001, a molecule that prevents development of gut permeability, ameliorates arthritis.
  • [1.36
    - Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis. - Aa has been proposed as a link between periodontitis and autoimmunity in rheumatoid arthritis (RA) due to its ability to induce citrullinated autoantigens targeted by anti-citrullinated protein antibodies (ACPAs).
  • [1.12
    - #Collinsella is increased in patients with rheumatoid arthritis and is associated with increased gut permeability.
  • [1.20
    -IgG and IgA autoantibodies from individuals who are at risk for RA cross-react against gut bacteria in the #Lachnospiraceae and #Ruminococcaceae families. - Analysis identified a bacterial strain from the #Subdoligranulum genus that was associated with autoantibody development. - Mice colonized with this #Subdoligranulum isolate developed arthritis with pathology similar to human RA.
  • [1.37
    - When compared with controls, participants with RA had increased levels of the Collinsella aerofaciens species and enterococcus genera. Likewise, an increase of arginine deaminase activity was observed, which belonged, in approximately 90%, to the RA genes of the genus Collinsela.

Common References