Relationship between postprandial metabolomics and colon motility in children with constipation

Authors

  • L. Rodriguez,

    Corresponding author
    • Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
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  • L. D. Roberts,

    1. Department of Medicine, Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • J. LaRosa,

    1. Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
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  • N. Heinz,

    1. Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
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  • R. Gerszten,

    1. Department of Medicine, Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • S. Nurko,

    1. Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology Children's Hospital Boston, Harvard Medical School, Boston, MA, USA
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  • A. M. Goldstein

    1. Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Address for Correspondence

Leonel Rodriguez, M.D., M.S., Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.

Tel: +617 355 6055; fax: +617 730 0043;

e-mail: leonel.rodriguez@childrens.harvard.edu

Abstract

Background

The metabolic pathways associated with colonic motility are unknown. To identify potential metabolic targets for treatment of constipation, we examined the metabolic profile before and after a meal challenge in a cohort of children with constipation and determined its relationship with postprandial colon motility patterns.

Methods

In this prospective study, 187 metabolites were measured by liquid chromatography–mass spectrometry at multiple time points before and after a standardized meal in constipated children undergoing a colon manometry. Postprandial metabolite levels were compared with baseline and also correlated with multiple manometric measurements, including the number, frequency, and amplitude of pressure peaks as well as the motility index (MI).

Key Results

A total of 20 subjects were included (mean age 13.1 ± 3.4 years). No significant metabolite changes were observed at 10 min after the meal, whereas 16 amino acid and 22 lipid metabolites had significant (P < 0.005) postprandial changes, including decreases in methylhistamine, histamine, and GABA, by 60 min. Correlations were observed between normal and abnormal postprandial motility patterns and changes in specific metabolites, including glycerol, carnosine, alanine, asparagine, cytosine, choline, phosphocholine, thyroxine, and triiodothyronine. Interestingly, subjects without the normal postprandial increase in area under the curve (AUC), had markedly increased levels of kynurenic acid and adenosyl-homocysteine.

Conclusions & Inferences

This is the first study to examine postprandial metabolic changes in children and also to correlate changes in specific metabolites with colonic motility. The results suggest possible metabolic pathways associated with motility and identify potential targets for the treatment of constipation.

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