Age and Fecal Microbial Strain-Specific Differences in Patients With Spondyloarthritis

Matthew L. Stoll; Pamela F. Weiss; Jennifer E. Weiss; Peter A. Nigrovic; Barbara S. Edelheit; S. Lou Bridges Jr; Maria I. Danila; Charles H. Spencer; Marilynn G. Punaro; Kenneth Schikler; Andreas Reiff; Ranjit Kumar; Randy Q. Cron; Casey D. Morrow; Elliot J. Lefkowitz

Disclosures

Arthritis Res Ther. 2018;20(14) 

In This Article

Background

The role of the intestinal microbiota in the pathogenesis of spondyloarthritis (SpA) is gaining widespread interest.[1] Much of this interest was spurred by a large body of literature indicating abnormalities of the microbiota in patients with inflammatory bowel disease (IBD),[2] a condition in which therapeutic alteration of the microbiota in the form of antibiotics, probiotics, and even fecal transplant may be effective,[3] along with the clinical and genetic associations between IBD and SpA.[4] Prior studies evaluating fecal or mucosal microbiota of adult patients with SpA demonstrated diminished fecal abundance of Bacteroides,[5,6] with one study showing a potential association between the Dialister genus and disease severity.[6] There are comparatively few data reported in pediatric SpA. One study showed decreased abundance of Prevotella in pediatric SpA,[7] and our prior work showed decreased abundance of Faecalibacterium prausnitzii.[8] The latter finding is consistent with multiple similar reports in subjects with IBD.[9] Depletion of F. prausnitzii may adversely impact intestinal health through diminished production of butyrate and other short chain fatty acids,[10] and our previous work has shown diminished abundance of butyrate in the fecal water of children with ERA.[11] Both pediatric SpA studies also showed increased abundance of unspecified species within the Bacteroides genus, consistent with studies in children with other categories of juvenile idiopathic arthritis (JIA),[12,13] yet the opposite of findings in adult subjects with rheumatoid arthritis (RA)[14,15] or SpA.[5,6]

Herein, we studied the intestinal microbiota in children with treatment-naïve SpA in comparison to pediatric healthy controls; to do this, we used a novel bioinformatics tool in combination with the Basic Local Alignment Search Tool (BLAST) that permitted assessment of species and even strain-level identification of certain organisms, as different strains within a species can have dramatically different effects.[16,17] In order to validate our prior results and to further increase the sample size, we recruited subjects from geographic locations around the country. Prior studies have shown that geography can impact the microbiota in situations in which subjects with highly different environments (e.g., urban versus rural) and ethnicities are compared,[18,19] but there are no data evaluating subjects from different urban areas specifically within the United States. The findings in these subjects were compared with those in adults with longstanding SpA and adult controls, to identify which changes might be common to SpA and which might be unique to pediatric populations. We also performed shotgun metagenomics sequencing on a subset of children with juvenile SpA in order to obtain additional information regarding potential mechanisms whereby the microbiota might predispose to SpA. Herein, we demonstrate that the anti-inflammatory A2-165 strain of F. prausnitzii is depleted in both pediatric and adult SpA, and that the microbiota of children with SpA has decreased genetic capacity to synthesize butyrate. We additionally demonstrate that B. fragilis is depleted in adult SpA yet abundant in pediatric disease.

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