Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn's disease

Horace R. T. Williams, I. Jane Cox, David G. Walker, Jeremy F. L. Cobbold, Simon D. Taylor-Robinson, Sara E. Marshall, Timothy R. Orchard

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    Abstract

    Background: Certain urinary metabolites are the product of gut microbial or mammalian metabolism; others, such as hippurate, are mammalian-microbial 'co-metabolites'. It has previously been observed that Crohn's disease (CD) patients excrete significantly less hippurate than controls. There are two stages in the biosynthesis of this metabolite: 1) gut microbial metabolism of dietary aromatic compounds to benzoate, and 2) subsequent hepatorenal conjugation of benzoate with glycine, forming hippurate. Differences in such urinary co-metabolites may therefore reflect systemic consequences of altered gut microbial metabolism, though altered host metabolic pathways may also be involved.

    Methods: It was hypothesised that reduced hippurate excretion in CD patients was due to alterations in the gut microbiota, and not differences in dietary benzoate, nor defective host enzymatic conjugation of benzoate. 5 mg/kg sodium benzoate were administered orally to 16 CD patients and 16 healthy controls on a low-benzoate diet. Baseline and peak urinary hippurate excretion were measured.

    Results: Baseline hippurate levels were significantly lower in the CD patients (p = 0.0009). After benzoate ingestion, peak urinary levels of hippurate did not differ significantly between the cohorts. Consequently the relative increase in excretion was significantly greater in CD (p = 0.0007).

    Conclusions: Lower urinary hippurate levels in CD are not due to differences in dietary benzoate. A defect in the enzymatic conjugation of benzoate in CD has been excluded, strongly implicating altered gut microbial metabolism as the cause of decreased hippurate levels in CD.

    Original languageEnglish
    Article number108
    Pages (from-to)-
    Number of pages8
    JournalBMC Gastroenterology
    Volume10
    DOIs
    Publication statusPublished - 17 Sep 2010

    Keywords

    • Inflammatory bowel disease
    • Benzoic acid
    • Sodium benzoate
    • Black tea
    • Green tea
    • Excretion
    • Metabonomics
    • Pathogenesis
    • Consumption
    • Ingestion

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