Another Look at the Contribution of Oral Microbiota to the Pathogenesis of Rheumatoid Arthritis: A Narrative Review

Berthelot, Jean‐Marie; Bandiaky, Octave Nadile; Goff, Benoît Le; Amador, Gilles; Chaux, Anne-Gaelle; Soueidan, Assem; Denis, Frédéric

doi:10.3390/microorganisms10010059

Cited by 16 publications

(19 citation statements)

References 94 publications

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“…The gut microbiome has increasingly emerged as a critical player in the onset and progression of RA 24. Notably, studies have revealed that changes in the gut microbiota composition are involved in the pathophysiology of RA 8 25 26.…”

Section: Discussionmentioning

confidence: 99%

Gut commensalParabacteroides distasonisalleviates inflammatory arthritis

Sun

Guo

Wang

et al. 2023

Gut

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ObjectiveGut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.DesignMicrobiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensalParabacteroides distasonisin RA. The effects ofP. distasonis-derived microbial metabolites on the differentiation of CD4+T cells and macrophage polarisation were also investigated.ResultsThe relative abundance ofP. distasonisin new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with liveP. distasonis(LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth ofP. distasonis.ConclusionsP. distasonisand ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.

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Section: Discussionmentioning

confidence: 99%

Gut commensalParabacteroides distasonisalleviates inflammatory arthritis

Sun

Guo

Wang

et al. 2023

Gut

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“…However, neither P. gingivalis nor A. actinomycetemcomitans was related to the alveolar bone loss or severity of arthritis in a mouse model [ 7 ]. It is suggested that persistent bacterial translocations from the oral cavity to the gut would increase intestinal permeability, resulting in penetration of oral bacteria into blood, triggering synovial autoimmunity in RA [ 8 ]. However, P. gingivalis might hardly survive the trip to the gut in humans [ 9 ] although it could translocate from a gingival site to stool in a mouse model of arthritis [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, P. gingivalis might hardly survive the trip to the gut in humans [ 9 ] although it could translocate from a gingival site to stool in a mouse model of arthritis [ 10 ]. Therefore, it was proposed that other oral microbes might be associated with the pathogenesis and progression of RA [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis

Chen

Hung

Chou

et al. 2022

IJMS

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Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3–V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production.

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Section: Introductionmentioning

confidence: 99%

“…Contribution of the oral microbiota to the etiopathogenesis of RA was recently discussed by Berthelot et al [ 13 ]. They stated that a growing body of evidence supports that oral bacteria, such as Porphyromonas gingivalis , contribute to the pathogenesis of RA, although the genetic background of patients may also play a role [ 13 ]. Studies relying on the high-throughput sequencing 16S ribosomal DNA gene ampliconspointed to Prevotella as a periodontal taxa of interest among the oral microbiota of patients with RA [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Oral Microbiota on the Presence of IgA Anti-Citrullinated Protein Antibodies in Gingival Crevicular Fluid

Smit

Rahajoe

Raveling-Eelsing

et al. 2022

Front. Oral. Health

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IntroductionThe relation between rheumatoid arthritis (RA) and periodontitis (PD) has been investigated ever since the discovery of the citrullinating enzyme peptidyl arginine deaminase presents in the oral bacterium Porphyromonas gingivalis. Recently, we demonstrated the presence of RA autoantibodies, especially of IgA anti-citrullinated protein antibody (ACPA), in gingival crevicular fluid (GCF) of Indonesian patients with and without RA or PD which might indicate the local formation of RA antibodies in the periodontium.AimThe purpose of this study was to assess whether the subgingival microbiome is related to the presence of IgA ACPA in the GCF of healthy individuals with or without PD.Patients and MethodsHealthy individuals with a known periodontal status and high IgA ACPA (>0.1 U/ml) in GCF (n = 27) were selected and matched for age, gender, periodontal status, and smoking status with 27 healthy individuals without IgA ACPA in their GCF. Taxonomic profiling of the subgingival microbiome was based on bacterial 16S rRNA gene sequencing. Downstream analyses were performed to assess compositional differences between healthy subjects with or without IgA ACPA in GCF and with or without PD.ResultsBetween groups with or without PD, or with or without IgA ACPA in GCF, no differences in alpha diversity were seen. Beta diversity was different between groups with or without PD (p < 0.0001), and a trend was seen in subjects with PD between subjects with or without IgA ACPA in GCF (p = 0.084). Linear discriminant analysis effect size (LEfSe) revealed no significant differences in the total population between subjects with IgA ACPA compared to subjects without IgA ACPA in GCF. Although Porphyromonas was not identified by LEfSe, its relative abundance was significantly higher in healthy individuals with high IgA ACPA in GCF compared to individuals without IgA ACPA in GCF (p = 0.0363). Zooming in on the subgroup with PD, LEfSe revealed that species Neisseriaceae, Tannerella, and Haemophilus were more abundant in the subjects with IgA ACPA in GCF compared to subjects without IgA ACPA in GCF.ConclusionPeriodontitis and certain taxa, including Porphyromonas, seem to be associated with the local presence of ACPA in the periodontium.

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Another Look at the Contribution of Oral Microbiota to the Pathogenesis of Rheumatoid Arthritis: A Narrative Review

Cited by 16 publications

References 94 publications

Gut commensalParabacteroides distasonisalleviates inflammatory arthritis

Gut commensalParabacteroides distasonisalleviates inflammatory arthritis

Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis

Influence of Oral Microbiota on the Presence of IgA Anti-Citrullinated Protein Antibodies in Gingival Crevicular Fluid

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