Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of<i>Clostridia</i>spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia

Shaw, W. M.

doi:10.1179/147683010x12611460763968

Cited by 134 publications

(98 citation statements)

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“…The tumor promoting activities of p -cresol and related compounds have been known for decades (Boutwell et al 1959). In addition to p -cresol, we observed 3-(3-hydroxyphenyl)-3-hydroxypropionate, a metabolite that has been associated with members of Clostridiae (Shaw 2010), to be elevated in colon cancer patients’ urine compared to rectal cancer patients’ urine. Moreover, urinary butyrate levels were increased in late-stage CRC patients prior to surgery.…”

Section: Discussionmentioning

confidence: 91%

Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare)

et al. 2014

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Introduction Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). We aimed to describe changes in the metabolome in the longer clinical follow-up and describe initial predictors as candidate markers with possibly prognostic significance Methods In total, 199 urine samples from CRC patients pre-surgery (n=97), 1–8 days post-surgery (n=12) and then after 6 and 12 months (n=52 and 38, respectively) were analyzed using both GC-MS and 1H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed. Results Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC. We were able to differentiate the metabolite profiles of CRC patients prior to surgery from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC=0.89; 95% CI:0.84–0.95). Conclusion To the best of our knowledge, this is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case-control studies and pin point metabolites which may serve as candidates for prognostic biomarkers of CRC.

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Section: Discussionmentioning

confidence: 91%

Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare)

et al. 2014

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“…8) [157]. 3 -Hydroxy-phenylhydracrylic acid has been identified as a phenylalanine catabolite of incompletely characterised metronidazole-sensitive bacteria [162], and proposed as a urinary biomarker for a range of neurological, gastrointestinal, and psychiatric disorders [163], and 4 -hydroxyphenylhydracrylic acid has been observed in patients with gastro-intestinal disease [164]. The definitive answer to the origin and significance of phenylhydracrylic acids is still lacking, but it has been shown that some Bacillus spp.…”

Section: Controls Used In Model Fermentations Have Clearly Demonstratmentioning

confidence: 99%

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

Williamson

Clifford

2017

Biochemical Pharmacology

271

172

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Please cite this article as: G. Williamson, M.N. Clifford, Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols, Biochemical Pharmacology (2017), doi: http://dx.doi.org/10.1016/ j. bcp.2017.03.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1Role of the small intestine, colon and microbiota in determining the metabolic fate of in the small intestine, or reaches the colon and is subject to extensive catabolism by colonic microbiota. Untransformed substrates may be absorbed, appearing in plasma primarily as methylated, sulfated and glucuronidated derivatives, with in some cases the unchanged substrate. Many of the catabolites are well absorbed from the colon and appear in the plasma either similarly conjugated, or as glycine conjugates, or in some cases unchanged.Although many (poly)phenol catabolites have been identified in human plasma and / or urine, the pathways from substrate to final catabolite, and the species of bacteria and enzymes involved, are still scarcely reported. While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol-rich commodities, such modulation is definitely not an inevitable consequence of supplementation, it depends on the treatment, length of time and on the individual metabotype, and it is not clear whether the modulation is sustained when supplementation ceases. Some catabolites have been recorded in plasma of volunteers at concentrations similar to those shown to be effective in in vitro studies suggesting that some benefit may be achieved in vivo by diets yielding such catabolites. and are also present at high levels in supplements [4], and form essential components of many Chinese medicines [5]. A study within the European Prospective Investigation intoCancer and Nutrition (EPIC) using the Phenol Explorer database reported that the cohort studied consumed 427 different polyphenols including 94 that were consumed at a rate of >1 g/day. The estimated total polyphenol consumption ranged from 584 mg/day by Greek women to 1786 mg/day for men in Aarhus-Denmark. The corresponding data for Greek men and for Aarhus women were 744 mg/day and 1626 mg/ day, respectively, with all data adjusted for age and weighted by season and weekday of dietary recall [6]. This study defined the major contributors to be the phenolic acids (predominantly the caffeoylquinic acids (27-53%), also called chlorogenic acids) and flavonoids (predominantly flavanols (16-29%), proanthocyanidins (5-9%) and theaflavins (14-25%)) [6]. Hydroxybenzoic acids (3.3-7.4%), alkyl-phenols (1.6...

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“…It was proposed that these metabolites were produced by the gut bacteria. High concentrations of an abnormal phenylalanine metabolite have been found in the urine of people with autism and schizophrenia, up to 300x normal adult values, which is likely due to multiple species of anaerobic bacteria in the Clostridium genus [73]. Others have detected abnormally high concentrations of hippurate in the urine in association with autism [74].…”

Section: Gut Dysbiosis Autism and Colitismentioning

confidence: 99%

Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases

Samsel

Seneff²

2013

Entropy

251

180

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Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite ofClostridiaspp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia

Cited by 134 publications

References 35 publications

Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare)

Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare)

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases

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