Gut microbiome in children with enthesitis-related arthritis in a developing country and the effect of probiotic administration

Abstract

In Asia, enthesitis-related arthritis (ERA) is the most frequent category of juvenile idiopathic arthritis. ERA has a strong association with human leucocyte antigen (HLA)-B27 and subclinical gut inflammation. In an HLA-B27 transgenic rat model, the presence of Bacteroides bacteria in the gut appears to cause spondyloarthropathy (SpA). Thus, we studied gut microbiota in children with ERA. Stool specimens from 33 patients with ERA and 14 age-matched healthy controls were studied; none had any gastrointestinal symptom, or had received a drug known to affect gut motility or microbiota in the preceding 6 weeks. From each specimen, a cDNA library for the V3 region of bacterial 16S rRNA was subjected to high-throughput, massively parallel sequencing. Relationship of the specimens was studied using principal co-ordinate analysis (PCoA), and abundances of various bacterial taxa and alpha diversity were compared between groups. In eight patients, a repeat faecal specimen was studied after 12 weeks of probiotic therapy. The 55 specimens yielded a median (range) of 397 315 (102 093-1 502 380) high-quality reads each. In PCoA, gut microbiota from ERA showed a wider dispersion than those from controls. In patients, families Bacteroidaceae and Enterobacteriaceae were more abundant and Prevotellaceae were less abundant than in controls. Also, genera Bacteroides, Entercoccus and Klebsiella were over-represented and genus Prevotella was under-represented in ERA patients. Probiotic therapy led to a non-significant increase in Prevotellaceae. Patients with ERA have a dysbiosis in the gut, with increased abundance of Bacteroides and reduction of Prevotella. Probiotic supplementation in a subset of patients did not reverse these changes significantly.

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…The selection of probiotics may need to be based not on what works in IBD, but rather on the demonstrated deficiencies in the target population, for example, children with JIA. This was not the case in the Aggarwal study, in which several of the bacteria that constitute VSL # 3 were normal if not elevated in the ERA population compared to the controls (Table ) …”

“…The following year, Aggarwal et al studied a cohort of Indian children with ERA (n = 33) compared to age‐matched healthy controls (n = 14) using 16S rRNA sequencing of the V3 region. They reported in the ERA patients a strong depletion of the Prevotellaceae family (66.5% vs 9.0%, P = .06) accompanied by increased abundance of the Bacteroides (0.06% vs 3.05%, P = .01) genus.…”

“…Finally, there will clearly be geographic variation in microbial associations with JIA. For example, Aggarwal et al reported increased abundance of Klebsiella in patients with ERA. It has long been posited that this organism may be responsible for ankylosing spondylitis, yet none of the prior studies in adult or pediatric SpA patients had identified this organism as being differentially abundant, or even present at all .…”

“…To better evaluate geographic and category factors associated with JIA, we performed a re‐analysis of previously published data of samples obtained in the USA, Finland, and India, obtaining fastq files and sample metadata from the respective authors. The USA and Indian samples were limited to ERA patients and healthy controls, while the Finnish data consisted mostly of oligo‐ and polyarticular JIA patients as well as healthy controls.…”

“…It should not be taken for granted that they will; a study of probiotic administration to mice demonstrated minimal uptake anywhere in their gastrointestinal tract, with a parallel study in humans demonstrating marked inter‐individual variability . Moreover, the study in children with ERA likewise demonstrated that the post‐intervention fecal specimens were not appreciably altered by the administration of the probiotic (Table ). Perhaps, then, therapeutic probiotics need to be preceded with antibiotics in order to facilitate uptake of the probiotics, as has been suggested for fecal transplant .…”