Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn's disease.
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.
Williams
Horace R T
HR
Department of Medicine, St Mary's Hospital, Imperial College London, UK. h.williams@imperial.ac.uk
Cox
I Jane
IJ
Walker
David G
DG
Cobbold
Jeremy F L
JF
Taylor-Robinson
Simon D
SD
Marshall
Sara E
SE
Orchard
Timothy R
TR
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006626:Hippurates / Q000652:urine*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020160:Sodium Benzoate / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
D006626:Hippurates; D020160:Sodium Benzoate; C030514:hippuric acid