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

BMC Gastroenterology

Research Article

Sara E Marshall¹  Horace RT Williams²  David G Walker²  Jeremy FL Cobbold²  Timothy R Orchard²  Simon D Taylor-Robinson²  I Jane Cox³ 

[1] Department of Immunology, University of Dundee, Dundee, UK;Gastroenterology and Hepatology Section, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK;Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital Campus, Imperial College London, London, UK;

关键词: Inflammatory Bowel Disease;    Intestinal Microbiota;    Control Cohort;    Healthy Control Individual;    Sodium Benzoate;   

DOI  :  10.1186/1471-230X-10-108

 received in 2010-07-22, accepted in 2010-09-17,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCertain 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.MethodsIt 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.ResultsBaseline 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).ConclusionsLower 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.

【 授权许可】

CC BY   
© Williams et al; licensee BioMed Central Ltd. 2010