Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli
Abstract Background Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13229-018-0218-4 |
| _version_ | 1818327270200180736 |
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| author | Stephen Bent Brittany Lawton Tracy Warren Felicia Widjaja Katherine Dang Jed W. Fahey Brian Cornblatt Jason M. Kinchen Kevin Delucchi Robert L. Hendren |
| author_facet | Stephen Bent Brittany Lawton Tracy Warren Felicia Widjaja Katherine Dang Jed W. Fahey Brian Cornblatt Jason M. Kinchen Kevin Delucchi Robert L. Hendren |
| author_sort | Stephen Bent |
| collection | DOAJ |
| description | Abstract Background Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds, was recently shown to lead to improvements in behavior and social responsiveness in children with ASD. We conducted the current open-label study to determine if we could identify changes in urinary metabolites that were associated with clinical improvements with the goal of identifying a potential mechanism of action. Methods Children and young adults enrolled in a school for children with ASD and related neurodevelopmental disorders were recruited to participate in a 12-week, open-label study of sulforaphane. Fasting urinary metabolites and measures of behavior (Aberrant Behavior Checklist—ABC) and social responsiveness (Social Responsiveness Scale—SRS) were measured at baseline and at the end of the study. Pearson’s correlation coefficient was calculated for the pre- to post-intervention change in each of the two clinical scales (ABS and SRS) versus the change in each metabolite. Results Fifteen children completed the 12-week study. Mean scores on both symptom measures showed improvements (decreases) over the study period, but only the change in the SRS was significant. The ABC improved − 7.1 points (95% CI − 17.4 to 3.2), and the SRS improved − 9.7 points (95% CI − 18.7 to − 0.8). We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism. Conclusions Urinary metabolomics analysis is a useful tool to identify pathways that may be involved in the mechanism of action of treatments targeting abnormal physiology in ASD. Trial registration This study was prospectively registered at clinicaltrials.gov (NCT02654743) on January 11, 2016. |
| first_indexed | 2024-12-13T12:13:36Z |
| format | Article |
| id | doaj.art-4ae4943e44a44211881f4e1cb7cb39e4 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-13T12:13:36Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-4ae4943e44a44211881f4e1cb7cb39e42022-12-21T23:46:46ZengBMCMolecular Autism2040-23922018-05-019111210.1186/s13229-018-0218-4Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoliStephen Bent0Brittany Lawton1Tracy Warren2Felicia Widjaja3Katherine Dang4Jed W. Fahey5Brian Cornblatt6Jason M. Kinchen7Kevin Delucchi8Robert L. Hendren9Department of Psychiatry, University of California, San FranciscoDepartment of Psychiatry, University of California, San FranciscoDepartment of Psychiatry, University of California, San FranciscoDepartment of Psychiatry, University of California, San FranciscoDepartment of Epidemiology and Biostatistics, University of California, San FranciscoDepartments of Medicine, Pharmacology and Molecular Sciences, International Health, and Cullman Chemoprotection Center, Johns Hopkins UniversityNutramax Laboratories Consumer Care, IncMetabolon, IncDepartment of Psychiatry, University of California, San FranciscoDepartment of Psychiatry, University of California, San FranciscoAbstract Background Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds, was recently shown to lead to improvements in behavior and social responsiveness in children with ASD. We conducted the current open-label study to determine if we could identify changes in urinary metabolites that were associated with clinical improvements with the goal of identifying a potential mechanism of action. Methods Children and young adults enrolled in a school for children with ASD and related neurodevelopmental disorders were recruited to participate in a 12-week, open-label study of sulforaphane. Fasting urinary metabolites and measures of behavior (Aberrant Behavior Checklist—ABC) and social responsiveness (Social Responsiveness Scale—SRS) were measured at baseline and at the end of the study. Pearson’s correlation coefficient was calculated for the pre- to post-intervention change in each of the two clinical scales (ABS and SRS) versus the change in each metabolite. Results Fifteen children completed the 12-week study. Mean scores on both symptom measures showed improvements (decreases) over the study period, but only the change in the SRS was significant. The ABC improved − 7.1 points (95% CI − 17.4 to 3.2), and the SRS improved − 9.7 points (95% CI − 18.7 to − 0.8). We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism. Conclusions Urinary metabolomics analysis is a useful tool to identify pathways that may be involved in the mechanism of action of treatments targeting abnormal physiology in ASD. Trial registration This study was prospectively registered at clinicaltrials.gov (NCT02654743) on January 11, 2016.http://link.springer.com/article/10.1186/s13229-018-0218-4AutismMetabolomicsAntioxidantBiomarker |
| spellingShingle | Stephen Bent Brittany Lawton Tracy Warren Felicia Widjaja Katherine Dang Jed W. Fahey Brian Cornblatt Jason M. Kinchen Kevin Delucchi Robert L. Hendren Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli Molecular Autism Autism Metabolomics Antioxidant Biomarker |
| title | Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli |
| title_full | Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli |
| title_fullStr | Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli |
| title_full_unstemmed | Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli |
| title_short | Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli |
| title_sort | identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli |
| topic | Autism Metabolomics Antioxidant Biomarker |
| url | http://link.springer.com/article/10.1186/s13229-018-0218-4 |
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