Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors

OBJECTIVE: We have previously shown alterations in the composition of the gut microbiota in children with enthesitis-related arthritis (ERA). To explore the mechanisms by which an altered microbiota might predispose to arthritis, we performed metabolomic profiling of fecal samples of children with ERA. METHODS: Fecal samples were collected from two cohorts of children with ERA and healthy control subjects. Nano-liquid chromatography – mass spectroscopy (LC-MS) was performed on the fecal water homogenates with identification based upon mass: charge ratios. Sequencing of the 16S ribosomal DNA (rDNA) on the same stool specimens was performed. RESULTS: In both sets of subjects, patients demonstrated lower diversity of ions and under-representation of multiple metabolic pathways, including the tryptophan metabolism pathway. For example, in the first cohort, out of 1,500 negatively charged ions, 154 were lower in ERA patients, compared to only one that was higher. Imputed functional annotation of the 16S rDNA sequence data demonstrated significantly fewer microbial genes associated with metabolic processes in the patients compared to the controls (77 million versus 58 million, p = 0.050.) CONCLUSIONS: Diminished metabolic diversity and alterations in the tryptophan metabolism pathway may be a feature of ERA.