Multivariate Analysis of Metabolomic and Nutritional Profiles among Children with Autism Spectrum Disorder

Abstract

There have been promising results regarding the capability of statistical and machine-learning techniques to offer insight into unique metabolomic patterns observed in ASD. This work re-examines a comparative study contrasting metabolomic and nutrient measurements of children with ASD (n = 55) against their typically developing (TD) peers (n = 44) through a multivariate statistical lens. Hypothesis testing, receiver characteristic curve assessment, and correlation analysis were consistent with prior work and served to underscore prominent areas where metabolomic and nutritional profiles between the groups diverged. Improved univariate analysis revealed 46 nutritional/metabolic differences that were significantly different between ASD and TD groups, with individual areas under the receiver operator curve (AUROC) scores of 0.6–0.9. Many of the significant measurements had correlations with many others, forming two integrated networks of interrelated metabolic differences in ASD. The TD group had 189 significant correlation pairs between metabolites, vs. only 106 for the ASD group, calling attention to underlying differences in metabolic processes. Furthermore, multivariate techniques identified potential biomarker panels with up to six metabolites that were able to attain a predictive accuracy of up to 98% for discriminating between ASD and TD, following cross-validation. Assessing all optimized multivariate models demonstrated concordance with prior physiological pathways identified in the literature, with some of the most important metabolites for discriminating ASD and TD being sulfate, the transsulfuration pathway, uridine (methylation biomarker), and beta-amino isobutyrate (regulator of carbohydrate and lipid metabolism).

Metabolomic changes in children with autism

“…The diet plays a significant role in shaping the metabolome, and the dietary patterns directly impact metabolic profiles in children with ASD. Studies on metabolomics have identified differences in nutrient intake and metabolism between individuals with ASD and typically developing individuals[ 223 , 224 ]. In individuals with ASD, amino acid metabolism, lipid metabolism, and energy metabolism alterations have been observed[ 225 ].…”

Ratings of the Effectiveness of 13 Therapeutic Diets for Autism Spectrum Disorder: Results of a National Survey

“…ASD involves many more comorbidities and underlying factors for which dietary intervention may be helpful, such as mitochondrial dysfunction [24], gastrointestinal issues, immune system dysregulation, seizures, and sleep disturbances, as well as psychological conditions including anxiety, depression and behavior problems [3]. Further abnormalities include oxidative stress [25] disordered methylation, sulfation, and transsulfuration [26], and disordered oxalate metabolism [27].…”

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood

“…These processes might result in metabolic dysregulations that can be observed in cord blood, detectable through metabolomics prior to the manifestation of autistic traits in early childhood. Multiple cross-sectional metabolomics studies among pre-school children with an ASD diagnosis and typically developing children have been conducted and suggested that mitochondrial dysfunction, immune dysregulation, as well as altered amino acid, lipid, and neurotransmitter metabolism could be associated with ASD [6][7][8][9][10][11][12][13][14][15][16][17][18]. Only one previous study assessed the prospective associations of stored dried blood spot metabolites in a small group of 37 newborns that received an ASD diagnosis in childhood and in healthy controls.…”