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

Genes & Immunity volume 17, pages 400–405 (2016)Cite this article

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Abstract

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. 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. 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 1500 negatively charged ions, 154 were lower in ERA patients, compared with only one that was higher. Imputed functional annotation of the 16S ribosomal DNA sequence data demonstrated significantly fewer microbial genes associated with metabolic processes in the patients compared with the controls (77 million versus 58 million, P=0.050). Diminished metabolic diversity and alterations in the tryptophan metabolism pathway may be a feature of ERA.

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Acknowledgements

This work was supported by the National Institutes of Health (Grant numbers P60 AR064172, P30AR050948, P30AI027767, UL1TR000165, S10 RR027822) and the American College of Rheumatology, Rheumatology Research Foundation. The following are acknowledged for their support of the Microbiome Resource at the University of Alabama at Birmingham: the School of Medicine, the Comprehensive Cancer Center (P30CA13148), the Center for AIDS Research (5P30AI027767), the Center for Clinical Translational Science (UL1TR000165) and the Heflin Center. We acknowledge Drs Peter Eipers and Anna Genin for their assistance with the preparation of the stool specimens and Landon Wilson for his assistance with metabolomics analysis.

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Authors and Affiliations

  1. Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    M L Stoll & R Q Cron

  2. Department of Center for Clinical and Translational Sciences, UAB, Birmingham, AL, USA

    R Kumar

  3. Department of Microbiology, UAB, Birmingham, AL, USA

    E J Lefkowitz

  4. Department of Cell, Developmental, and Integrative Biology, UAB, Birmingham, AL, USA

    C D Morrow

  5. Department of Pharmacology, UAB, Birmingham, AL, USA

    S Barnes

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  1. M L Stoll
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Correspondence to M L Stoll.

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Stoll, M., Kumar, R., Lefkowitz, E. et al. Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors. Genes Immun 17, 400–405 (2016). https://doi.org/10.1038/gene.2016.38

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