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

Abstract

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.

Microbiome Analytics of the Gut Microbiota in Patients With Juvenile Idiopathic Arthritis: A Longitudinal Observational Cohort Study

“…Additionally, in a cohort of patients with the enthesitis‐related arthritis (ERA) subtype of JIA compared to healthy controls, differences in community structure were predicted to decrease metabolic functions. In the same cohort, a lower diversity of ions and underrepresentation of the tryptophan metabolic pathway was observed in patients . Tryptophan metabolites can lead to the production of proinflammatory cytokines, thus potentially linking the gut microbiota with inflammation .…”

“…In the same cohort, a lower diversity of ions and underrepresentation of the tryptophan metabolic pathway was observed in patients . Tryptophan metabolites can lead to the production of proinflammatory cytokines, thus potentially linking the gut microbiota with inflammation . In another cohort of ERA patients, predicted functions of the gut microbiota were related to cell motility and chemotaxis .…”

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

“…These analyses revealed an under‐representation of multiple metabolic pathways, including the tryptophan metabolism pathway. Significantly fewer microbial genes associated with metabolic processes in the patients compared with the controls were observed, indicating diminished metabolic diversity as a potential feature of JIA‐ERA …”

“…Significantly fewer microbial genes associated with metabolic processes in the patients compared with the controls were observed, indicating diminished metabolic diversity as a potential feature of JIA-ERA. 80 A study in an Italian cohort of 29 patients with JIA (19 with JIA-ERA and 10 with JIA-non ERA) in comparison to 29 healthy controls, identified differences in various bacterial families belonging to the Firmicutes phyla. 81 In particular, in comparison to healthy subjects, Ruminococcaceae resulted as increased in patients with JIA, Veillonellaceae in JIA-non ERA, whereas Clostridiaceae and Peptostreptococcaceae were decreased in JIA-ERA.…”

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…This could result in decreased production of butyrate, which is an important substrate for gut epithelial cells and can also directly induce the differentiation of regulatory T cells . It is thus of particular interest that Stoll et al also demonstrated decreased microbial genetic potential to synthesize butyrate as well as decreased fecal water representation of the butyrate pathway …”