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Intestinal microbiota, metabolome and gender dimorphism in autism spectrum disorders / Rafail I. KUSHAK in Research in Autism Spectrum Disorders, 49 (May 2018)
[article]
Titre : Intestinal microbiota, metabolome and gender dimorphism in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Rafail I. KUSHAK, Auteur ; Harland S. WINTER, Auteur Article en page(s) : p.65-74 Langues : Anglais (eng) Mots-clés : Autism Gender Microbiota Metabolome Gut-brain interactions Index. décimale : PER Périodiques Résumé : There is a male predominance in autism, with a male/female ratio of 4:1 and an even higher ratio (11:1) in individuals with high functioning autism. The reasons for gender differences in ASD are unknown. Genetic and environmental factors have been implicated, but no definitive evidence exists to explain male predominance. In this review, evidence is presented to support a hypothesis that the intestinal microbiota and metabolome play a role in gender dimorphism in children with autism. Metabolic products may affect not only gastrointestinal (GI) tract and the central nervous system, but also behavior, supporting communication between GI tract and central nervous system. Furthermore, mood and anxiety may affect intestinal function, indicating bidirectional flow in the gut-brain axis. Several hormone-based hypotheses are discussed to explain the prevalence of autism in males. Observations in animal models and studies in humans on the intestinal microbiome and metabolome are reviewed to support the proposed gender dimorphism hypothesis. We hypothesize that the intestinal microbiome is a contributing factor to the prevalence of ASD in boys either directly, through microbial metabolites and/or epigenetic factors capable of regulating host gene expression through DNA methylation and/or histone modification. En ligne : https://doi.org/10.1016/j.rasd.2018.01.009 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=340
in Research in Autism Spectrum Disorders > 49 (May 2018) . - p.65-74[article] Intestinal microbiota, metabolome and gender dimorphism in autism spectrum disorders [Texte imprimé et/ou numérique] / Rafail I. KUSHAK, Auteur ; Harland S. WINTER, Auteur . - p.65-74.
Langues : Anglais (eng)
in Research in Autism Spectrum Disorders > 49 (May 2018) . - p.65-74
Mots-clés : Autism Gender Microbiota Metabolome Gut-brain interactions Index. décimale : PER Périodiques Résumé : There is a male predominance in autism, with a male/female ratio of 4:1 and an even higher ratio (11:1) in individuals with high functioning autism. The reasons for gender differences in ASD are unknown. Genetic and environmental factors have been implicated, but no definitive evidence exists to explain male predominance. In this review, evidence is presented to support a hypothesis that the intestinal microbiota and metabolome play a role in gender dimorphism in children with autism. Metabolic products may affect not only gastrointestinal (GI) tract and the central nervous system, but also behavior, supporting communication between GI tract and central nervous system. Furthermore, mood and anxiety may affect intestinal function, indicating bidirectional flow in the gut-brain axis. Several hormone-based hypotheses are discussed to explain the prevalence of autism in males. Observations in animal models and studies in humans on the intestinal microbiome and metabolome are reviewed to support the proposed gender dimorphism hypothesis. We hypothesize that the intestinal microbiome is a contributing factor to the prevalence of ASD in boys either directly, through microbial metabolites and/or epigenetic factors capable of regulating host gene expression through DNA methylation and/or histone modification. En ligne : https://doi.org/10.1016/j.rasd.2018.01.009 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=340 Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder / Jiang ZHU in Journal of Autism and Developmental Disorders, 52-7 (July 2022)
[article]
Titre : Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Jiang ZHU, Auteur ; Xueying HUA, Auteur ; Ting YANG, Auteur ; Min GUO, Auteur ; Qiu LI, Auteur ; Lu XIAO, Auteur ; Ling LI, Auteur ; Jie CHEN, Auteur ; Tingyu LI, Auteur Article en page(s) : p.3116-3128 Langues : Anglais (eng) Mots-clés : Amino Acids/metabolism Autism Spectrum Disorder/diagnosis Child Humans Intestines Metabolome Metabolomics/methods Vitamins Autism Children Metabolism Metabolomics Symptoms Vitamin Index. décimale : PER Périodiques Résumé : Metabolic disturbance may be implicated in the pathogenesis of autism. This study aimed to investigate the gut metabolomic profiles of autistic children and to analyze potential interaction between gut metabolites with autistic symptoms and neurodevelopment levels. We involved 120 autistic and 60 neurotypical children. Autistic symptoms and neurodevelopment levels were assessed. Fecal samples were analyzed using untargeted liquid chromatography-tandem mass spectrometry methods. Our results showed the metabolic disturbances of autistic children involved in multiple vitamin and amino acid metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine-methionine metabolism, and vitamin digestion and absorption. Differential gut metabolites were correlated to autistic symptoms and neurodevelopment levels. Our findings improved the understanding of the perturbations of metabolome networks in autism. En ligne : http://dx.doi.org/10.1007/s10803-021-05066-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477
in Journal of Autism and Developmental Disorders > 52-7 (July 2022) . - p.3116-3128[article] Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Jiang ZHU, Auteur ; Xueying HUA, Auteur ; Ting YANG, Auteur ; Min GUO, Auteur ; Qiu LI, Auteur ; Lu XIAO, Auteur ; Ling LI, Auteur ; Jie CHEN, Auteur ; Tingyu LI, Auteur . - p.3116-3128.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 52-7 (July 2022) . - p.3116-3128
Mots-clés : Amino Acids/metabolism Autism Spectrum Disorder/diagnosis Child Humans Intestines Metabolome Metabolomics/methods Vitamins Autism Children Metabolism Metabolomics Symptoms Vitamin Index. décimale : PER Périodiques Résumé : Metabolic disturbance may be implicated in the pathogenesis of autism. This study aimed to investigate the gut metabolomic profiles of autistic children and to analyze potential interaction between gut metabolites with autistic symptoms and neurodevelopment levels. We involved 120 autistic and 60 neurotypical children. Autistic symptoms and neurodevelopment levels were assessed. Fecal samples were analyzed using untargeted liquid chromatography-tandem mass spectrometry methods. Our results showed the metabolic disturbances of autistic children involved in multiple vitamin and amino acid metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine-methionine metabolism, and vitamin digestion and absorption. Differential gut metabolites were correlated to autistic symptoms and neurodevelopment levels. Our findings improved the understanding of the perturbations of metabolome networks in autism. En ligne : http://dx.doi.org/10.1007/s10803-021-05066-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli / Stephen BENT in Molecular Autism, 9 (2018)
[article]
Titre : Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli Type de document : Texte imprimé et/ou numérique Auteurs : Stephen BENT, Auteur ; B. LAWTON, Auteur ; T. WARREN, Auteur ; F. WIDJAJA, Auteur ; K. DANG, Auteur ; J. W. FAHEY, Auteur ; Brian CORNBLATT, Auteur ; J. M. KINCHEN, Auteur ; K. DELUCCHI, Auteur ; R. L. HENDREN, Auteur Article en page(s) : 35p. Langues : Anglais (eng) Mots-clés : Adolescent Antioxidants/administration & dosage/analysis/therapeutic use Autistic Disorder/drug therapy/urine Biomarkers/urine Brassica/chemistry Child Female Humans Isothiocyanates/administration & dosage/analysis/therapeutic use Male Metabolome Social Behavior Young Adult Antioxidant Autism Biomarker Metabolomics Index. décimale : PER Périodiques Résumé : 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. En ligne : https://dx.doi.org/10.1186/s13229-018-0218-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 35p.[article] Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli [Texte imprimé et/ou numérique] / Stephen BENT, Auteur ; B. LAWTON, Auteur ; T. WARREN, Auteur ; F. WIDJAJA, Auteur ; K. DANG, Auteur ; J. W. FAHEY, Auteur ; Brian CORNBLATT, Auteur ; J. M. KINCHEN, Auteur ; K. DELUCCHI, Auteur ; R. L. HENDREN, Auteur . - 35p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 35p.
Mots-clés : Adolescent Antioxidants/administration & dosage/analysis/therapeutic use Autistic Disorder/drug therapy/urine Biomarkers/urine Brassica/chemistry Child Female Humans Isothiocyanates/administration & dosage/analysis/therapeutic use Male Metabolome Social Behavior Young Adult Antioxidant Autism Biomarker Metabolomics Index. décimale : PER Périodiques Résumé : 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. En ligne : https://dx.doi.org/10.1186/s13229-018-0218-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder: a prospective birth cohort study / N. S. ANAND in Journal of Child Psychology and Psychiatry, 62-7 (July 2021)
[article]
Titre : Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder: a prospective birth cohort study Type de document : Texte imprimé et/ou numérique Auteurs : N. S. ANAND, Auteur ; Y. JI, Auteur ; G. WANG, Auteur ; X. HONG, Auteur ; M. VAN DER RIJN, Auteur ; A. RILEY, Auteur ; C. PEARSON, Auteur ; Barry S. ZUCKERMAN, Auteur ; X. WANG, Auteur Article en page(s) : p.868-875 Langues : Anglais (eng) Mots-clés : Amino Acids, Branched-Chain Attention Deficit Disorder with Hyperactivity/epidemiology Child Cohort Studies Female Humans Infant, Newborn Pregnancy Premature Birth Prospective Studies Attention-Deficit Hyperactivity Disorder branched-chain amino acids cord blood metabolome Index. décimale : PER Périodiques Résumé : BACKGROUND: Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are essential amino acids involved in biological functions of brain development and recently linked with autism. However, their role in attention-deficit hyperactivity disorder (ADHD) is not well-studied. We investigated individual and combined relationships of maternal plasma and newborn cord plasma BCAAs with childhood development of ADHD. METHODS: We utilized the Boston Birth Cohort, a predominantly urban, low-income, US minority population. Child developmental outcomes were defined in three mutually exclusive groups - ADHD, neurotypical (NT), or other developmental disabilities based on physician diagnoses per ICD-9 or 10 in medical records. The final sample included 626 children (299 ADHD, 327 NT) excluding other developmental disabilities. BCAAs were measured by liquid chromatography-tandem mass spectrometry. We used factor analysis to create composite scores of maternal and cord BCAA, which we divided into tertiles. Logistic regressions analyzed relationships between maternal or cord BCAA tertiles with child ADHD risk, controlling for maternal race, age, parity, smoking, education, low birth weight, preterm birth, and child sex. Additionally, we analyzed maternal and cord plasma BCAAs jointly on child ADHD risk. RESULTS: Adjusted logistic regression found significantly increased odds of child ADHD diagnosis for the second (OR 1.63, 95% CI: 1.04, 2.54, p = .032) and third tertiles (OR 2.01, 95% CI: 1.28, 3.15, p = .002) of cord BCAA scores compared to the first tertile. This finding held for the third tertile when further adjusting for maternal BCAA score. There was no significant association between maternal BCAA score and child ADHD risk, nor a significant interaction between maternal and cord BCAA scores. CONCLUSIONS: In this prospective US birth cohort, higher cord BCAA levels were associated with a greater risk of developing ADHD in childhood. These results have implications for further research into mechanisms of ADHD development and possible early life screening and interventions. En ligne : http://dx.doi.org/10.1111/jcpp.13332 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456
in Journal of Child Psychology and Psychiatry > 62-7 (July 2021) . - p.868-875[article] Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder: a prospective birth cohort study [Texte imprimé et/ou numérique] / N. S. ANAND, Auteur ; Y. JI, Auteur ; G. WANG, Auteur ; X. HONG, Auteur ; M. VAN DER RIJN, Auteur ; A. RILEY, Auteur ; C. PEARSON, Auteur ; Barry S. ZUCKERMAN, Auteur ; X. WANG, Auteur . - p.868-875.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 62-7 (July 2021) . - p.868-875
Mots-clés : Amino Acids, Branched-Chain Attention Deficit Disorder with Hyperactivity/epidemiology Child Cohort Studies Female Humans Infant, Newborn Pregnancy Premature Birth Prospective Studies Attention-Deficit Hyperactivity Disorder branched-chain amino acids cord blood metabolome Index. décimale : PER Périodiques Résumé : BACKGROUND: Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are essential amino acids involved in biological functions of brain development and recently linked with autism. However, their role in attention-deficit hyperactivity disorder (ADHD) is not well-studied. We investigated individual and combined relationships of maternal plasma and newborn cord plasma BCAAs with childhood development of ADHD. METHODS: We utilized the Boston Birth Cohort, a predominantly urban, low-income, US minority population. Child developmental outcomes were defined in three mutually exclusive groups - ADHD, neurotypical (NT), or other developmental disabilities based on physician diagnoses per ICD-9 or 10 in medical records. The final sample included 626 children (299 ADHD, 327 NT) excluding other developmental disabilities. BCAAs were measured by liquid chromatography-tandem mass spectrometry. We used factor analysis to create composite scores of maternal and cord BCAA, which we divided into tertiles. Logistic regressions analyzed relationships between maternal or cord BCAA tertiles with child ADHD risk, controlling for maternal race, age, parity, smoking, education, low birth weight, preterm birth, and child sex. Additionally, we analyzed maternal and cord plasma BCAAs jointly on child ADHD risk. RESULTS: Adjusted logistic regression found significantly increased odds of child ADHD diagnosis for the second (OR 1.63, 95% CI: 1.04, 2.54, p = .032) and third tertiles (OR 2.01, 95% CI: 1.28, 3.15, p = .002) of cord BCAA scores compared to the first tertile. This finding held for the third tertile when further adjusting for maternal BCAA score. There was no significant association between maternal BCAA score and child ADHD risk, nor a significant interaction between maternal and cord BCAA scores. CONCLUSIONS: In this prospective US birth cohort, higher cord BCAA levels were associated with a greater risk of developing ADHD in childhood. These results have implications for further research into mechanisms of ADHD development and possible early life screening and interventions. En ligne : http://dx.doi.org/10.1111/jcpp.13332 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456