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Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia
Abstract
A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.
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“Altered patterns of bacterial metabolites were seen in a large number of children with ASD compared to healthy control children. These metabolites included elevated 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), a catabolic byproduct of Clostridia [59].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [59]
Citations
Cites
Goodman and Gilman's the Pharmacological Basis of Therapeutics
Stigelman, W. H., & Pharm, D. (1986) · Military Medicine · doi:10.1093/milmed/151.1.386 · Cited by 6,796
Harrison's Principles of Internal Medicine.
(1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-100-1-167_1 · Cited by 1,527
Zheng, W., & Wang, S. Y. (2002) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf020728u · Cited by 814
Parracho, H. M., Bingham, M. O., Gibson, G. R., & McCartney, A. L. (2005) · Journal of Medical Microbiology · doi:10.1099/jmm.0.46101-0 · Cited by 784
Gastrointestinal Microflora Studies in Late‐Onset Autism
Finegold, S. M., Molitoris, D., Song, Y., Liu, C., Vaisanen, M., Bolte, E., McTeague, M., Sandler, R., Wexler, H., Marlowe, E. M., et al. (2002) · Clinical Infectious Diseases · doi:10.1086/341914 · Cited by 742
Short-Term Benefit From Oral Vancomycin Treatment of Regressive-Onset Autism
Sandler, R. H., Finegold, S. M., Bolte, E. R., Buchanan, C. P., Maxwell, A. P., Väisänen, M.-L., Nelson, M. N., & Wexler, H. M. (2000) · Journal of Child Neurology · doi:10.1177/088307380001500701 · Cited by 614
Major Phenolics in Apple and Their Contribution to the Total Antioxidant Capacity
Lee, K. W., Kim, Y. J., Kim, D., Lee, H. J., & Lee, C. Y. (2003) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf034475w · Cited by 611
Real-Time PCR Quantitation of Clostridia in Feces of Autistic Children
Song, Y., Liu, C., & Finegold, S. M. (2004) · Applied and Environmental Microbiology · doi:10.1128/aem.70.11.6459-6465.2004 · Cited by 556
SUCCESSFUL TREATMENT OF RELAPSING CLOSTRIDIUM DIFFICILE COLITIS WITH LACTOBACILLUS GG
Gorbach, S., Chang, T., & Goldin, B. R. (1987) · The Lancet · doi:10.1016/s0140-6736(87)92646-8 · Cited by 467
Antibiotic-Associated Diarrhea
Bartlett, J. G. (1992) · Clinical Infectious Diseases · doi:10.1093/clind/15.4.573 · Cited by 414
Research works printed but not linked: 6
- Finegold S, 1986, Scand J Infect Dis, 49, 160
- Rollo I, 1970, Goodman and Gilmans The Pharmacological Basis of Therapeutics
- 1993, The Physicians Desk Reference
- Kirby WM, 1983, Harrisons Principles of Internal Medicine, 872
- Waring R, 1993, Biological Perspectives in Autism Conference, 25
- Conway P, 1995, Human Colonic Bacteria, 1
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Blachier, F. (2023) · Springer eBooks · doi:10.1007/978-3-031-26322-4_5 · Cited by 2
Chen, L., Li, W., Mo, D., Meng, X., Yao, L., Zhang, X., & Liu, H. (2025) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s523570 · Cited by 2
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Ortíz, G. G., Bitzer-Quintero, O. K., Ramírez-Jirano, L. J., Pacheco-Moisés, F. P., González-Usigli, H., Torres-Mendoza, B. M., Mireles-Ramírez, M. A., Torres-Sánchez, E. D., & Delgado-Lara, D. L. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99336-4.00009-4
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Wang, H., Zhou, Y., Zhao, M., Li, S., Wen, Y., Wang, K., Wang, M., Tian, J., Xiang, W., Chen, C., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3383550/v1 · Cited by 1
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Bindal, P., Kaushal, S., Singh, C., & Singh, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-21680-0.00005-5
Sullivan, D. L. (2015) · ScholarWorks (Walden University)
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585535
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585550
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585538
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585544
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585532
AL-Ayadhi, L. Y., Zayed, N., Bhat, R. S., Moubayed, N. M. S., Al-Muammar, M. N., & El-Ansary, A. (2021) · Figshare · doi:10.6084/m9.figshare.16614539
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585541
d’Oplinter, A. D. W., Verce, M., Huwart, S. J. P., Lessard‐Lord, J., Depommier, C., Hul, M. V., Desjardins, Y., Cani, P. D., & Everard, A. (2024) · Figshare · doi:10.6084/m9.figshare.26585547
Greenblatt, J. M., & ROUNTREE, R. L. (2026) · Integrative and Complementary Therapies · doi:10.1177/27683192261419213
Chen, C., He, J., Ma, Z., Na, W., Cao, Y., Li, B., He, Z., Yuan, H., Xiao, H., Wang, S., et al. (2026) · The Journal of Headache and Pain · doi:10.1186/s10194-026-02360-9
Babolin, S., Enea, R., Cicala, M., Giovanni, D. D., Mazzone, L., & Gialloreti, L. E. (2026) · BMC Psychiatry · doi:10.1186/s12888-026-08178-8
Verçosa, G. D., Dariani, G. G., Chaves, D. P., Lelis, G. C., Fonseca, W. T., Merces, L., Braunger, M. L., & de Oliveira, R. F. (2026) · ACS Applied Nano Materials · doi:10.1021/acsanm.6c02147
Metadata
- Authors
- Shaw, W.
- Corresponding author
- Shaw, William
- Venue
- Nutritional Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2010-06
- Volume
- 13
- Issue
- 3
- Pages
- 135-143
- ISSN
- 1028-415X (ISSN-L)
- 1476-8305
- OpenAlex
- W2016430945
- Cited by
- 162
- References
- 41
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 11 · 2023: 8 · 2022: 12 · 2021: 17 · 2020: 15 · 2019: 18 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 11 · 2014: 8 · 2013: 6 · 2012: 3
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutritional Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- urinary biomarkers, autism spectrum disorder, schizophrenia, Clostridium, Clostridium difficile infection, m-tyrosine, phenylalanine metabolism, vancomycin, anaerobic gut bacteria, catecholamine depletion
- MeSH terms
- Acute Disease, Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Clostridium, Clostridium Infections, Enterocolitis, Pseudomembranous, Female, Humans, Male, Middle Aged, Phenylalanine, Phenylpropionates, Schizophrenia, Sex Characteristics, Vancomycin, Clostridioides difficile, Gastrointestinal Tract, Young Adult
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