Background/Purpose: Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota in pediatric and adult patients with spondyloarthritis (SpA.) In particular, diminished fecal abundance of Faecalibacterium prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified, mirroring results in studies of patients with inflammatory bowel disease.

Methods: We obtained fecal specimens from children with treatment-naïve enthesitis-related arthritis (ERA) and healthy controls from multiple geographic locations, as well as specimens from adult patients with long-standing SpA. All of the samples underwent sequencing of the 16S ribosomal DNA (rDNA). A subset of the ERA and healthy pediatric fecal samples were also subjected to shotgun metagenomics sequencing.

Results: Children with ERA (n = 30) and healthy controls (n = 19) underwent 16S rDNA sequencing. Clustering of the microbiota based upon diagnosis (p = 0.046) was observed, while among ERA patients, there was no clustering by geographic location. In contrast to previous studies, fecal abundance of F. prausnitzii was slightly higher in the patients versus controls (10.0% vs 7.8%, p = 0.192); however strain-level differences were observed, with patients having relatively decreased abundance of the anti-inflammatory A2-165 strain (41% versus 54%, p = 0.084) and an increased abundance of the control L2/6 strain (28% versus 15%, p = 0.038). Similar trends were observed in adults with long-standing SpA (n = 11) and controls (n = 10): total F. prausniztii 10% in patients versus 6.9% in controls (p = 0.427), while A2-165 as percentage of F. prausnitzii was 25% in patients versus 41% in controls (p = 0.175).

With respect to B. fragilis, opposite trends were seen among the pediatric versus the adult subjects. Specifically, pediatric patients with ERA demonstrated increased abundance of B. fragilis compared to controls (2.0% versus 0.45%, p = 0.045), yet adult subjects demonstrated decreased abundance of the Bacteroides genus (11% versus 26%, p = 0.036) and specifically of B. fragilis (0.2% versus 1%, p = 0.106).

Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects did not demonstrate any global pathway differences. However, it did reveal diminished coverage of the butanoate pathway (abundance normalized to controls of 1 versus 0.72 in ERA, p = 0.037).

Conclusion: Our study supports previous work indicating that decreased fecal abundance of a regulatory strain of F. prausnitzii may be at least partly responsible for the pathogenesis of SpA, possibly due to decreased production of butyrate, and suggests that efforts to replenish it in patients with SpA may be a potential therapeutic avenue. In contrast, the mechanism by which Bacteroides impacts arthritis may differ in pediatric and adult patients, possibly reflecting altered immunologic development in the former rather than direct pathogenicity or the organism. If this is the case, then enthusiasm for microbial-based interventions to address this organism may be tempered. Instead, our findings may underscore the necessity of prevention efforts, such as avoiding unnecessary use of antibiotics in healthy children.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/children-with-treatment-naive-enthesitis-related-arthritis-have-decreased-fecal-abundance-of-faecalibacterium-prausnitzii-a2-165-and-bacteroides-fragilis-a-multi-center-collaborative-study/