Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine

Maeda, Yukihide; Kurakawa, Takashi; Umemoto, Eiji; Motooka, Daisuke; Ito, Yoshinaga; Gotoh, Kazuyoshi; Hirota, Keiji; Matsushita, M.; Furuta, Yoshikazu; Narazaki, Masashi; Sakaguchi, Noriko; Kayama, Hisako; Nakamura, Shota; Iida, Tetsuya; Saeki, Yukihiko; Kumanogoh, Atsushi; Sakaguchi, Shimon; Takeda, Kiyoshi

doi:10.1002/art.39783

Cited by 493 publications

(474 citation statements)

References 48 publications

(66 reference statements)

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“…This genus appears to have effects on intestinal T helper 17 cells, 26 and it has been found to be increased in faecal samples from patients with CD, 27 28 and new-onset rheumatoid arthritis. 29 Also consistent with our prior study, the abundance of the pathobiont genera, Fusobacterium, and uncommon γ-Proteobacteria (eg, Erwinia) were higher in the UCLA-SSc faecal samples compared with controls.…”

Section: Discussionmentioning

confidence: 99%

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts

Volkmann

Hoffmann‐Vold

Chang

et al. 2017

BMJ Open Gastroenterol

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ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5–16.4) and 7.0 (1.0–19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state.

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Section: Discussionmentioning

confidence: 99%

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts

Volkmann

Hoffmann‐Vold

Chang

et al. 2017

BMJ Open Gastroenterol

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“…), including P. copri, in the gut microbiota were expanded in stool samples from patients with new-onset RA (NORA), suggesting that these organisms might have this role in RA pathogenesis (13). Moreover, a recent study in mice showed that gut dysbiosis contributes to arthritis development via the activation of autoreactive T cells in the intestine (15). Proposed mechanisms to link infection and autoimmunity include molecular mimicry between T cell microbial and host epitopes (16); infection-induced alteration and release of sequestered self-antigens (11); or nonspecific, infectioninduced inflammatory responses that function as adjuvants in the induction of pathogenic autoimmunity (17,18).…”

Section: Introductionmentioning

confidence: 99%

Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints

Pianta

Arvikar

Strle

et al. 2017

Journal of Clinical Investigation

164

116

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“…We have shown that some Japanese RA patients carry increased numbers of Prevotella copri in the intestine and have used gnotobiotic tools to show that a P. copri -dominated microbiota induced Th17 cell-dependent arthritis in mice [12]. In contrast, another study showed that P. histicola suppresses the development of arthritis [13].…”

Section: Introductionmentioning

confidence: 99%

Role of Gut Microbiota in Rheumatoid Arthritis

Maeda

Takeda

2017

JCM

Self Cite

165

114

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Rheumatoid arthritis (RA) is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gut microbiota in RA. We and others have demonstrated that the abundance of Prevotella copri is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, Prevotella histicola from human gut microbiota suppressed the development of arthritis. In summary, Prevotella species are involved in the pathogenesis of arthritis.

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Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine

Cited by 493 publications

References 48 publications

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts

Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints

Role of Gut Microbiota in Rheumatoid Arthritis

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