Abstract
Autism Spectrum Disorder (ASD) affects one in 87 to 126 children in Italy. This serious condition results from neurodevelopmental abnormalities due, in most cases, to a polygenic/oligogenic vulnerability, which can be influenced by environmental factors, especially in the prenatal and early postnatal period. Behavioral abnor-malities generally begin around 18 to 24 months of age. To date, the diagnosis of ASD is still based exclusively on observation of the child, and there are no biomarkers to support the clinical diagnosis of autism: it is not possible to predict whether a child will develop an ASD, whether they will develop expressive language or re-main nonverbal, or how they will respond to rehabilitative therapies. This project, which builds on a series of previous national and international projects, aims to identify the me-tabolites produced by the gut microbiota most strongly associated with ASD and to define the bacterial taxa related to their production. For years, we have studied the urinary metabolomics of children with ASD, com-paring them to their unaffected siblings and normotypic controls. We have also identified a compound derived primarily from gut bacteria, p-cresol, which is significantly more abundant in the urine of autistic children. To-gether with its metabolite, p-cresyl sulfate, it is a known uremic toxin with marked central and peripheral ad-verse effects. We recently demonstrated that a single administration of p-cresol in the BTBR mouse, a robust mouse model of ASD, can both exacerbate autism-like behaviors and induce anxiety and hyperactivity, the two most common comorbidities in human ASD. This project aims to consolidate and extend these findings by: (1) recruiting and clinically characterizing at least 150 children with ASD aged 3–8 years and 50 age- and sex-matched normotypic controls; (2) analysis of the urinary and fecal metabolome using hydrophilic interac-tion chromatography (HILIC)-UHPLC and mass spectrometry (MS); (3) parallel analysis of the urinary and fecal metabolome using nuclear magnetic resonance (NMR) spectroscopy on the same samples; (4) metagenomic analysis of the gut microbiota using partial 16S rRNA sequencing and correlation studies between microbiota composition, metabolites, and clinical parameters. The parallel use of MS and NMR to analyze the same samples will maximize the reliability of urinary and fecal metabolomics results. The data obtained from these studies will enable the development of targeted and in-novative interventions based on "smart foods" containing prebiotics, capable of reducing the intestinal pro-duction and/or absorption of the most pathogenic metabolites, subsequently quantifying their efficacy on au-tistic symptoms, as well as any synergistic effects with currently available therapies for ASD.
Dettagli del progetto
Responsabile scientifico: Francesco Capozzi
Strutture Unibo coinvolte:
Dipartimento di Scienze e Tecnologie Agro-Alimentari
Coordinatore:
Università degli studi di Modena e Reggio Emilia - UNIMORE(Italy)
Contributo totale Unibo: Euro (EUR) 51.503,00
Durata del progetto in mesi: 24
Data di inizio
18/10/2023
Data di fine:
28/02/2026
