Patients with juvenile idiopathic arthritis (JIA) demonstrated evidence of dysbiosis and reduced diversity in the gut microbiome compared with healthy controls, according to a report published in Arthritis & Rheumatology. Microbiota differences appeared to be driven by age, geography, and patient status, irrespective of autoimmunity markers, inflammation, or disease activity.
Autoimmune disorders, including JIA, have been associated with gut flora alterations, but the nature of the connection has remained unknown. Investigators sought to fill this knowledge gap by comparing the microbiome of those with and without JIA.
Between October 2013 and December 2015, a multicenter, prospective, observational cohort study recruited new-onset Italian and Dutch treatment-naive patients with JIA (with <6 months since symptom appearance) and geography-matched healthy controls, all of whom provided fecal samples at baseline. There were 78 Italian children (median age, 3.9 years; 78.2% female) and 21 Dutch children (median age, 8.5 years; 76.2% female) with JIA enrolled, along with 107 geography-matched healthy controls. Patients were assessed every 6 months over 2 years, and secondary follow-up was performed on 44 and 25 patients with JIA who displayed inactive disease and persistent activity, respectively.
Researchers used 16S rRNA metagenomic analysis to determine the composition of gut microbiota, calculating both α- and β-diversity. Random forest modelling and logistic regression analysis were used to compare relative abundance log-ratios between patients and controls.
In terms of α-diversity, at baseline, Italian patients had significantly reduced species richness compared with controls (β=-158; 95% CI, -219 to -97; P <.001); these differences were consistent during inactive disease and persistent disease activity. The same measure in Dutch patients offered weak evidence of enhanced richness in patients vs controls (β=76; 95% CI, 8-145; P =.03). Regarding β-diversity, at baseline, both the Italian (P =.001) and Dutch (P =.013) patient populations differed between patients and controls. Microbiome differences between patients and controls were confirmed in the Italian cohort and suggested in the Dutch cohort using random forest models, with areas under the curve of >0.99 and 0.71, respectively.
After multivariable adjustment, there were clear differences in the relative abundance of 3 operational taxonomic units of the 57 analyzed when comparing Italian patients and controls at baseline. Erysipelotrichaceae and Faecalibacterium prausnitzii were both increased in patients vs controls, whereas Allobaculum was decreased. Although raw data indicated some differences in relative abundance of operational taxonomic units between Dutch patients and controls, multivariate comparisons yielded no significant variations between groups. Paired analysis did not reveal any differences when comparing Italian patients at baseline with those later categorized as having inactive disease.
Study strengths included relatively large sample sizes, longitudinal analysis permitting comparison of microbiota in various states of disease activity, and the use of compositional data analysis. Study limitations included small subsamples of those with persistent activity or inactive disease and a limited number of paired samples.
“In conclusion, our results supported the hypothesis of gut dysbiosis in [patients with JIA], in terms of richness and compositional deviation from healthy subjects,” noted the authors. They recommended that future research focus on better age and sex matching, replication in additional populations, and clarification of potential causal mechanisms between dysbiosis and JIA.
van Dijkhuizen EHP, Del Chierico F, Malattia C, et al. Microbiome analytics of the gut microbiota in juvenile idiopathic arthritis patients: an observational, longitudinal cohort study [published online December 28, 2018]. Arthritis Rheumatol. doi:10.1002/art.40827