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The GEMMA Project

What is GEMMA?

Researchers at NUI Galway are partners in an EU consortium of researchers who have been awarded €14.2M funding by the European Commission as part of Horizon 2020 programme.  The project GEMMA (Genome, Environment, Microbiome and Metabolome in Autism) is a ground-breaking autism research project which will for the first time follow children who are at risk of developing autism from 6 months of age.

Autism Spectrum Conditions (ASC), which affect 1 in 59 children (1 in 37 boys and 1 in 151 girls) worldwide (a 40-fold increase since 1960), are a major concern for individuals, families and healthcare systems. The research community is struggling to understand the multifactorial risk factors leading to its onset. As of today, there are no proven biomarkers of ASC and diagnosis relies entirely on behavioural evaluations. Children born into a family with a sibling already has a diagnosis of ASC have a 10 times higher risk of developing ASC.


GEMMA will be the first project to combine a multi-omic approach with robust environmental data to exploit the analysis of the composition and function of the microbiome for personalized treatment in at-risk infants.


What are the aims of GEMMA?

GEMMA aims is to better understand the development of ASC symptoms over time. The average age of diagnosis in Ireland is 4-5 years of age.  However, ASC symptoms become apparent in the first few months of life.  We aim to study children from the age of 6-36 months of age and this may lead to earlier diagnosis than is currently possible.


Children with ASC commonly experience gastrointestinal symptoms such as chronic constipation, persistent diarrhoea, bloating, abdominal pain and discomfort, nausea, reflux and vomiting. It is clear that children with ASC who display gastrointestinal symptoms also express increased behavioural issues such as irritability, tantrums, and aggressive behaviour. GEMMA will study the relationship between the development of ASC and gastrointestinal symptoms.


GEMMA aims to identify biomarkers – measurable changes in the gut microbiota – that could predict development of ASC in genetically predisposed infants.  A further goal of GEMMA is to provide solid insights into ASC onset and its progression in relation to dynamic changes in abnormal gut microbiota.  This research may lead to personalised treatment plans and dietary interventions that will reduce gastrointestinal symptoms and potentially lower the risk of ASC.


What are the objectives of GEMMA?

Currently large-scale datasets in ASC are mostly cross-sectional studies (cases vs controls) that do not allow the mechanistic link between microbiome composition/function with ASC onset. Rather, prospective studies following infants at-risk from birth to identify potential biomarkers predictor of ASC development followed by validation on large multi-omic datasets are necessary. The 3 participant recruitment centres will allow a global sampling based on their geographical coverage (2 European centres (Ireland and Italy) and Massachusetts General Hospital for Children (MGH), a United States of America (US) partner) and their broad network covering over 9,500 families with ASC children, which will facilitate the recruitment of 600 infants at risk of ASC (new-borns in families already with a child with ASC).

Objective 1: To study modifications of the infants’ microbiome/metagenome/metatranscriptome in relation to their dietary regimen, intestinal permeability (determined by serum zonulin levels), immune response to dietary proteins (via IgA and IgG levels), and in relation to urine/stool metabolites and increased low-grade chronic inflammation (via serum pro-inflammatory cytokine) identifying biomarker predictors of ASC in at-risk infants.

Objective 2: To compare multi-omic biomarker evolution (disease modelling) between children that develop ASC with age-, sex-, and GI symptom-matched at-risk infants who did not develop ASC.

Objective 3: To identify pre-natal, peri-natal, and post-natal environmental risk factors associated with future onset of ASC.

Objective 4: To comprehend host-microbiome genomics in order to predict integrate biology networks leading to the activation of metabolic pathways mechanistically linked with functional (gut permeability, immune response) and clinical (ASC) outcomes.


What will happen in the GEMMA project?

Researchers plan to enrol 600 infants at risk of developing ASC at centres in Italy, Ireland and the U.S. Infants will be followed very closely from birth, to monitor their progress toward the possible onset of ASC. Collecting stool, tissue and blood samples from children over a 5-year period – along with environmental data – scientists will study the interaction of the gut microbiota (microbe community) and its related mechanisms with the intestinal barrier and immune response.

In the context of a unique EU-US collaboration network, the project results will be validated on large international ASC networks and integrated with large-scale omics data repositories. Clinical trial data will be shared and harmonized with other international, large-scale omic databases. This research will contribute to the overarching goals of determining the interaction between the dynamic changes over time of the microbiome with the genome and its epigenetic changes, the metabolome, mucosal integrity and immune response that lead to ASC.


GEMMA has assembled a team of scientists from EBRIS; Nutricia Research; Medinok; Bio-Modeling Systems; Euformatics; Theoreo SRL; National University of Ireland Galway; Azienda Sanitaria Locale Salerno; Massachusetts General Hospital for Children (teaching hospital of Harvard Medical School);Consiglio Nazionale delle Ricerche; INRA; INSERM; Utrecht University; University of Tampere; Imperial College London and John Hopkins University.

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