The urinary metabolomics profile of an Italian autistic children population and their unaffected siblings
Abstract
OBJECTIVE: A supervised multivariate model to classify the metabolome alterations between autistic spectrum disorders (ASD) patients and controls, siblings of autistic patients, has been realized and used to realize a network model of the ASD patients' metabolome. METHODS: In our experiment we propose a quantification of urinary metabolites with the Mass Spectroscopy technique couple to Gas Chromatography. A multivariate model has been used to extrapolate the variables of importance for a network model of interaction between metabolites. In this way we are able to propose a network-based approach to ASD description. RESULTS: Children with autistic disease composing our studied population showed elevated concentration of several organic acids and sugars. Interactions among diet, intestinal flora and genes may explain such findings. Among them, the 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid has been previously described as altered in autistic subjects. Other metabolites increased are 3,4-dihydroxybutyric acid, glycolic acid and glycine, cis-aconitic acid; phenylalanine, tyrosine, p-hydroxyphenylacetic acid, and homovanillic acid are all involved in the tyrosine pathway leading to neurotransmitter cathecolamine. CONCLUSION: GC-MS-based metabolomic analysis of the urinary metabolome suggests to have the required sensitivity and specificity to gain insight into ASD phenotypes and aid a personalized network-based medicine approach.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Metabolome studies have repeatedly shown evidence of alterations in tryptophan, kynurenine, and serotonin pathways in children with ASD, including increased urinary excretion of tryptophan and associated metabolites.
“Metabolome studies have repeatedly shown evidence of alterations in tryptophan, kynurenine, and serotonin pathways in children with ASD, including reports of increased urinary excretion of tryptophan and associated metabolites [63, 67, 68, 72, 105].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [67]
Cites
The Metabolic and Molecular Bases of Inherited Disease
Scriver, R. C. (1995) · Medical Entomology and Zoology · Cited by 12,101 · see citing works
The metabolic and molecular bases of inherited disease
Chen, Y.-T. (2001) · Medical Entomology and Zoology · Cited by 6,928 · see citing works
KEGG for integration and interpretation of large-scale molecular data sets
Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., & Tanabe, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr988 · Cited by 4,848 · see citing works
De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D. I., Cristofori, F., Guerzoni, M. E., Gobbetti, M., & Francavilla, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076993 · Cited by 887 · see citing works
Self-citationSchmidt, R. J., Tancredi, D. J., Ozonoff, S., Hansen, R. L., Hartiala, J., Allayee, H., Schmidt, L. C., Tassone, F., & Hertz-Picciotto, I. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.004416 · Cited by 408 · see citing works
Amminger, G. P., Berger, G. E., Schäfer, M. R., Klier, C., Friedrich, M. H., & Feucht, M. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.007 · Cited by 355 · see citing works
Yap, I. K. S., Angley, M. T., Veselkov, K., Holmes, E. C., Lindon, J. C., & Nicholson, J. K. (2010) · Journal of Proteome Research · doi:10.1021/pr901188e · Cited by 316 · see citing works
Roberts, A. L., Lyall, K., Hart, J. E., Laden, F., Just, A. C., Bobb, J. F., Koenen, K. C., Ascherio, A., & Weisskopf, M. G. (2013) · Environmental Health Perspectives · doi:10.1289/ehp.1206187 · Cited by 306 · see citing works
L-serine in disease and development.
de Koning, T. D., Snell, K., Durán, M., Berger, R., Poll-The, B., & Surtees, R. (2003) · Biochemical Journal · doi:10.1042/bj20021785 · Cited by 287 · see citing works
Metabolic Perturbance in Autism Spectrum Disorders: A Metabolomics Study
Ming, X., Stein, T. P., Barnes, V., Rhodes, N., & Guo, L. (2012) · Journal of Proteome Research · doi:10.1021/pr300910n · Cited by 234 · see citing works
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency
Pearl, P. L., Gibson, K. M., Acosta, M. T., Vezina, L. G., Theodore, W. H., Rogawski, M. A., Novotny, E. J., Gropman, A. L., Conry, J. A., Berry, G. T., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000059549.70717.80 · Cited by 203 · see citing works
An investigation of orthogonal signal correction algorithms and their characteristics
Svensson, O., Kourti, T., & MacGregor, J. F. (2002) · Journal of Chemometrics · doi:10.1002/cem.700 · Cited by 166 · see citing works
Shaw, W. (2010) · Nutritional Neuroscience · doi:10.1179/147683010x12611460763968 · Cited by 162 · see citing works
Huck, J. H. J., Verhoeven‐Duif, N. M., Struys, E. A., Salomons, G. S., Jakobs, C., & van der Knaap, M. S. (2004) · The American Journal of Human Genetics · doi:10.1086/383204 · Cited by 149 · see citing works
Autism Diagnostic Observation Schedule
Luyster, R. J. (2018) · The SAGE Encyclopedia of Intellectual and Developmental Disorders · doi:10.4135/9781483392271.n47 · Cited by 132 · see citing works
GC-MS-based urine metabolic profiling of autism spectrum disorders
Emond, P., Mavel, S., Aïdoud, N., Nadal‐Desbarats, L., Montigny, F., Bonnet‐Brilhault, F., Barthélémy, C., Merten, M. D., Sarda, P., Laumonnier, F., et al. (2013) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-013-6934-x · Cited by 112 · see citing works
Neuropathology of thiamine deficiency disorders
Kril, J. J. (1996) · Metabolic Brain Disease · doi:10.1007/bf02080928 · Cited by 105 · see citing works
The Primary Hyperoxalurias: An Algorithm for Diagnosis
Milliner, D. S. (2005) · American Journal of Nephrology · doi:10.1159/000085407 · Cited by 103 · see citing works
Autistic children exhibit distinct plasma amino acid profile.
Naushad, S. M., Jain, J. M. N., Prasad, C. K., Naik, U., & Akella, R. R. D. (2013) · PubMed · Cited by 65 · see citing works
Advantages of orthogonal inspection in chemometrics
Pinto, R. C., Trygg, J., & Gottfries, J. (2012) · Journal of Chemometrics · doi:10.1002/cem.2441 · Cited by 55 · see citing works
Gorman, S., Weeden, C. E., Tan, D. H. W., Scott, N. M., Hart, J., Foong, R. E., Mok, D., Stephens, N., Zosky, G. R., & Hart, P. H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067823 · Cited by 55 · see citing works
Purification and Characterization of d-Lyxose Isomerase
Anderson, R. L., & Allison, D. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97332-1 · Cited by 54 · see citing works
Serine metabolism and psychosis
Waziri, R., WILCOX, J. A., Sherman, A. D., & Mott, J. (1984) · Psychiatry Research · doi:10.1016/0165-1781(84)90012-x · Cited by 52 · see citing works
Detection and possible origins of aminomalonic acid in protein hydrolysates
Copley, S. D., Frank, E. A., Kirsch, W. M., et al. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90188-d · Cited by 46 · see citing works
Succinic Semialdehyde Dehydrogenase Deficiency
Gibson, K. M., Sweetman, L., Nyhan, W. L., et al. (1984) · Journal of Neurogenetics · doi:10.3109/01677068409107087 · Cited by 45 · see citing works
Shinka, T., Inoue, Y., Ohse, M., et al. (2002) · Journal of Chromatography B · doi:10.1016/s1570-0232(02)00126-5 · Cited by 40 · see citing works
Aminomalonic acid: identification in Escherichia coli and atherosclerotic plaque.
Buskirk, J. J. V., Kirsch, W. M., Kleyer, D. L., et al. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.3.722 · Cited by 37 · see citing works
SPE–NMR metabolite sub-profiling of urine
Jacobs, D. M., Spiesser, L., Garnier, M., de Roo, N., van Dorsten, F. A., Hollebrands, B., van Velzen, E. J. J., Draijer, R., & van Duynhoven, J. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-6339-2 · Cited by 36 · see citing works
Dyck, L. E., Kazakoff, C. W., & Dourish, C. T. (1982) · European Journal of Pharmacology · doi:10.1016/0014-2999(82)90196-0 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Autism Spectrum Disorders and the Gut Microbiota
Fattorusso, A., Di Genova, L., Dell’Isola, G., Mencaroni, E., & Esposito, S. (2019) · Nutrients · doi:10.3390/nu11030521 · Cited by 484 · see citing works
The Gut Microbiota and Autism Spectrum Disorders
Li, Q., Han, Y., Dy, A. B. C., & Hagerman, R. J. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00120 · Cited by 462 · see citing works
Dan, Z., Mao, X., Liu, Q., Guo, M., Zhuang, Y., Liu, Z., Chen, K., Chen, J., Xu, R., Tang, J., et al. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1747329 · Cited by 350 · see citing works
Autism spectrum disorders and intestinal microbiota
De Angelis, M., Francavilla, R., Piccolo, M., De Giacomo, A., & Gobbetti, M. (2015) · Gut Microbes · doi:10.1080/19490976.2015.1035855 · Cited by 311 · see citing works
Self-citationGevi, F., Zolla, L., Gabriele, S., & Persico, A. M. (2016) · Molecular Autism · doi:10.1186/s13229-016-0109-5 · Cited by 251 · see citing works
The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders
Hughes, H. K., Rose, D., & Ashwood, P. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0887-6 · Cited by 225 · see citing works
Diémé, B., Mavel, S., Blasco, H., Tripi, G., Bonnet-Brilhault, F., Malvy, J., Bocca, C., Andres, C. R., Nadal-Desbarats, L., & Emond, P. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00699 · Cited by 122 · see citing works
Dargenio, V. N., Dargenio, C., Castellaneta, S., De Giacomo, A., Laguardia, M., Schettini, F., Francavilla, R., & Cristofori, F. (2023) · Nutrients · doi:10.3390/nu15071620 · Cited by 98 · see citing works
Self-citationLussu, M., Noto, A., Masili, A., Rinaldi, A. C., Dessì, A., De Angelis, M., De Giacomo, A., Fanos, V., Atzori, L., & Francavilla, R. (2017) · Autism Research · doi:10.1002/aur.1748 · Cited by 67 · see citing works
Self-citationMetabolome signature of autism in the human prefrontal cortex
Kurochkin, I., Khrameeva, E., Tkachev, A., Stepanova, V., Vanyushkina, A., Stekolshchikova, E., Li, Q., Zubkov, D., Shichkova, P., Halene, T., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0485-4 · Cited by 57 · see citing works
- Authors
- Noto, A., Fanos, V., Barberini, L., Grapov, D., Fattuoni, C., Zaffanello, M., Casanova, A., Fenu, G., De Giacomo, A., De Angelis, M., Moretti, C., Papoff, P., Ditonno, R., & Francavilla, R.
- Affiliations
- University of Cagliari (IT)
- University of California, Davis (US)
- University of Verona (IT)
- Policlinico Umberto I (IT)
- University of Bari Aldo Moro (IT)
- Corresponding author
- Fanos, Vassilios
- ORCID
- Venue
- The Journal of Maternal-Fetal & Neonatal Medicine
- Publisher
- Informa UK Limited
- Published
- 2014-10
- Volume
- 27
- Issue
- sup2
- Pages
- 46-52
- ISSN
- 1476-4954 (ISSN-L)
- 1476-7058
- OpenAlex
- W1982265989
- Cited by
- 113
- References
- 29
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 12 · 2022: 15 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 15 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 1
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Maternal-Fetal & Neonatal Medicine (publishedVersion)
- PubMed (publishedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097154)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- autism spectrum disorder, urine metabolomics, organic acids, catecholamines, glycine, phenylalanine, homovanillic acid, diet and gut microbiota, children, unaffected siblings
- MeSH terms
- Adolescent, Autistic Disorder, Child, Child, Preschool, Female, Humans, Italy, Male, Gas Chromatography-Mass Spectrometry, Sensitivity and Specificity, Least-Squares Analysis, Siblings, Metabolomics, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
