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

BMC Gastroenterol. 2010 Sep 17;10:108. doi: 10.1186/1471-230X-10-108.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Bacteria / drug effects
  • Bacteria / metabolism*
  • Crohn Disease / drug therapy
  • Crohn Disease / metabolism*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Tract / microbiology*
  • Hippurates / urine*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Prognosis
  • Sodium Benzoate / administration & dosage
  • Sodium Benzoate / therapeutic use
  • Young Adult

Substances

  • Hippurates
  • Sodium Benzoate
  • hippuric acid