The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment

Abstract

We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.

Review: Preclinical Rheumatoid Arthritis: Progress Toward Prevention

“…Liu et al (36) Gut microbiome DMARD-naive patients with early RA had increased Lactobacillus abundance and diversity compared to healthy controls. Zhang et al (39) Gut microbiome Dysbiosis in the gut (and oral) microbiome of patients with RA was partially resolved after RA treatment; Lactobacillus salivarius was overrepresented in patients with RA, while Haemophilus strains were relatively depleted. Vaahtovuo et al (38) Bacterial diversity Widespread microbial differences found in intestinal microbiota of patients with early RA compared to patients with fibromyalgia.…”

“…Altering the local T cell balance in this way may lead to systemic autoimmunity. Indeed, several studies have demonstrated that gut dysbiosis occurs in RA (36)(37)(38)(39) and that specific bacteria, including Lactobacillus (36) and Prevotella copri (37), are more abundant in new, untreated RA patients.…”

“…Considering mucosal autoimmunity in this way, treatment of PD and mucosal dysbiosis may also alter disease risk. In RA patients, treatment of PD has been shown to improve disease severity (66), and oral and gut dysbiosis appears to improve following treatment with disease-modifying antirheumatic drugs (39). Whether similar success is achievable in preclinical disease remains to be seen and is certainly an exciting area for future research.…”

Investigating a holobiont: Microbiota perturbations and transkingdom networks

“…[52][53][54][55][56][57][58] Although most of them do not go beyond simple association tests, 2 approaches should be specifically mentioned as similarly to our method they attempt to pinpoint microbes that have potential causal effect on unrelated phenotype. 52,59 The first one, LEfSe, is a popular tool that has been already utilized by several groups.…”

The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases

“…Lactobacillus than that of the control group. In a recently published paper, compositional and functional alterations in RA-associated gut and oral microbiomes were observed, which were partly relieved by disease modifying anti-rheumatic drugs (DMARD) treatment [18]. To delineate the features of the RAassociated gut microbiome, the authors performed a microbiome genome-wide association study identifying 117,219 gene markers that were differentially enriched in RA patients and controls and clustered these genes into metagenomic linkage groups (MLGs) on the basis of their correlated abundance variation among samples.…”