GEMMA has received funding from the EU Horizon 2020 programme under Grant Agreement No 825033. GEMMA aims to employ an integrated multi-omic systems biology approach to identify biomarkers for personalized treatment and primary prevention of Autism Spectrum Disorders (ASD). The project plan will consist on recruiting 600 infants at risk of autism and analyze, at multi-omics level, their biological samples over a 36 month period along the project’s 5-years-period, followed by an interventional arm to manipulate the gut microbiome in order to mitigate infiammation both at the gastrointestinal level and in the brain of children that will develop ASD during the study. It has been widely demonstrated that ASD is not a single disorder, but a spectrum of related disorders with a shared core of symptoms defined by deficits in communication, social reciprocity and repetitive, stereotypic behaviors. ASD represent a significant public health issue since it dramatically increased in the last decades reaching the prevalence of 1 in 59 children around the world with a strong sex bias (4:1 male:female ratio). Moreover, it was found that in families with a children with ASD, the chances that a siblings will develop autism are around one in five, thus considering the presence of inherited risk factors. Many individuals with ASD suffer from associated co-morbidities (i.e. metabolic conditions, and gastrointestinal disorders), and the neuroanatomical and biochemical characteristics associated with autism pathogenesis involve mechanisms that are direct consequences of the effects of systemic inflammatory events. The scope of the project is to use high quality microbiome, metabolome, and other -omics data to link microbiome composition and function with specific disease for personalized prediction, prevention, and treatment of disease: the prospective study to identify potential biomarkers, able to predict ASD development followed by validation on large multi-omic datasets will be the main goal of GEMMA. 3 infants recruitment centers will allow a global sampling based on their geographical coverage (Europe and US) and their broad network, which will facilitate the recruitment of 600 newborns in families already with a child suffering from ASD. GEMMA workflow was based on two non-mutually exclusive hypotheses: the first, affirming that the gut bacterial dysbiosis leads to epigenetic modifications, changes in metabolite profiles, increased gut permeability, increased macromolecules trafficking and, ultimately, to altered immune responses to promote disease in a subset of individuals at-risk of ASD; the second, asserting that the genome/metagenome interplay is responsible for the switch from immune tolerance to immune response to environmental stimuli, including dietary and microbial factors leading to neuroinflammation responsible of behavioral changes that characterize ASD and gut inflammation causing its GI co-morbidities.
