Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

Abstract

Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.DOI: http://dx.doi.org/10.7554/eLife.01202.001

Smoking and Air Pollution as Pro-Inflammatory Triggers for the Development of Rheumatoid Arthritis

“…Potential mechanisms of initiation and/or exacerbation of RA included: i) deposition of bacterial endotoxin in the joints [5,6]; and ii) production of antibodies and cytotoxic T lymphocytes reactive with cross-reactive epitopes present on both the putative causative bacterial pathogens and host synovial autoantigens [7]. In keeping with these earlier studies, alterations in the GIT microbiome, resulting in replacement of beneficial commensals such as Bacteroides, Blautia, Lachnospiraceae and Group XIV Clostridia clades with the pro-inflammatory, Gram-negative, anaerobic rod, Prevotella copri have recently been linked to the pathogenesis of RA [8], possibly due to lifestyle factors such as diet and smoking [9].…”

Reciprocity in Microbiome and Immune System Interactions and its Implications in Disease and Health

“…Accordingly, the prevalance of P. copri in patients treated for rheumatoid arthrits is similar to healthy individuals [101]. Mice that are genetically prone to arthritis and colonized with P. copri are more susceptible to the experimental induction of colits with DSS [101].…”

“…Analysis of gut microbiota from patients with recentonset rheumatoid arthritis (RA) indicates that there is a strong association of the disease with the presense of Prevotella copri and reduction in Bacteroides and other beneficial gut bacteria [101]. Accordingly, the prevalance of P. copri in patients treated for rheumatoid arthrits is similar to healthy individuals [101].…”

“…Accordingly, the prevalance of P. copri in patients treated for rheumatoid arthrits is similar to healthy individuals [101]. Mice that are genetically prone to arthritis and colonized with P. copri are more susceptible to the experimental induction of colits with DSS [101]. In animal mouse models of arthritis, germ free mice do not develop arthritis but upon colonization with specific gut microbiota demonstrate joint inflammmation [26,102].…”

Investigating a holobiont: Microbiota perturbations and transkingdom networks

“…52,59 The first one, LEfSe, is a popular tool that has been already utilized by several groups. [60][61][62] More importantly a few studies went beyond analyses and successfully validated computational predictions of this approach. For example, LEfSe has been applied on 16S and shotgun metagenomics data to identify Prevotella copri to be related to Rheumatoid arthritis and experimentally proved to be able to increase inflammatory response in the gut.…”