Genome, Environment, Microbiome & Metabolome in Autism: an integrated multi-omic systems biology approach to identify biomarkers for personalized treatment and primary prevention of Autism Spectr

Project Information

GEMMA

Grant agreement ID: 825033

DOI 10.3030/825033

EC signature date 22 November 2018

Start date 1 January 2019

End date 31 December 2024

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost € 14 225 757,50

EU contribution € 14 225 757,50

Coordinated by

FONDAZIONE EBRIS
Italy

Deliverables

Documents, reports (11)

Report on the participation to the IHMC congress in Barcelona 2020

Report on the outcomes of the participation of GEMMA at the 8th International Human Microbiome Congress in 2020 (Barcelona)

Final clinical protocols

Study protocols to submit for the approbation to the ethical committee

Pre-clinical study 2 report

A report providing the results of the trial 2 to investigate if the ASD phenotype is dependent on microbiome-induced systemic immune activation, via adoptive splenocyte transfer studies

Theoretical qualitative models of ASD pathogenesis mechanisms

A model specifically detail the mechanisms whereby alterations in gut microbiome may lead to persistent, low-grade feverless systemic inflammation and how this could then affect CNS metabolism and neuronal arborescence preferentially in male developing infants

Pre-clinical study ethical approval report

A study protocol to submit for the approbation to the ethical committee

Pre-clinical study 1 report

A report providing the results of the the trial 1 focus on exploring if the behavioural phenotype of ASD patients is transferrable to mice via faecal transplantation

Genome, epigenome and immune function interplay summary of hypothesis

An hypothesis regarding how the genome/metagenome interplay is responsible for the switch from immune tolerance to immune response to environmental stimuli (antigens) including dietary and microbial factors leading to neuroinflammation responsible of behavioural changes that characterize ASD and gut inflammation causing its GI co-morbidities

Updated state of the art report

Report providing a brief relation about the state of the art in the ASD biomarker and therapy

Microbiome, metabolome and immune function interplay summary of hypothesis

An hypothesis regarding how the gut bacterial dysbiosis leads to epigenetic modifications, changes in metabolic profiles, increased gut permeability, increased antigen trafficking and, ultimately to altered immune responses to promote disease in a subset of individuals at-risk of ASD

Mid-term recruitment report

Statistical data on the enrollment process in the 3 different recruitment sites: number of subjects who were included at each site (frequency counts and percentages based on the number of subjects contributing data into the study), subject discontinuations and departures from the study protocol

Pre-clinical study 3/1 report

A first report providing the results of trial 3 to establish whether correction of dysbiosis by pre/pro/symbiotic intervention prevents and/or treats increased the impaired gut permeability, changes in metabolic profile, modification of the immune response, and, ultimately, the onset of ASD behavioural symptoms in humanized murine models of ASD (mice transplanted with faecal bacterial content of ASD patient donor sample

Demonstrators, pilots, prototypes (3)

First release of the multi-omics platform (pre-clinical trials)

An algorithms able to associate various biomarker levels observed in infants with ASD and GI symptoms. This alghorithm will use advanced statistical analysis methods such as sparse canonical correlation (a linear correlation method) combined with random forests (a non-linear correlation method) to detect these associations between the omics data.

Second release of the multi-omics platform (observational trials)

An analysis of the fitting between the correlations put forward by the multi-omics analyses and the biological outcome of the interventional part of the observational study

OmnomicsNGS v2 release

A new relase of the software OmnomicsNGS including a tool for dynamic variant analysis and interpretation

Open Research Data Pilot (1)

Open data management plan

GEMMA participation on H2020 open data pilot

Websites, patent fillings, videos etc. (1)

External project website

Project website: project description, public deliverables, scientific news, other

Publications

Peer reviewed articles (26)

An integrative network analysis framework for identifying molecular functions in complex disorders examining major depressive disorder as a test case.

Author(s): Oommen AM, Cunningham S, O'Súilleabháin PS, Hughes BM, Joshi L
Published in: Scientific Reports, Issue (2021) 11:9645, 2021, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-021-89040-7

Neurotensin-Binding Immunoglobulin G in Patients with Parkinson’s Disease

Author(s): Muruzheva ZM, Egorov DS, Absalyamova MT, Traktirov DS, Karpenko MN, and Fetissov SO
Published in: Neuroimmunomodulation, Issue 30(1), 2023, Page(s) 15-27, ISSN 1021-7401
Publisher: S. Karger AG
DOI: 10.1159/000527872

Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation

Author(s): Lyudmila V. Gromova, Serguei O. Fetissov, Andrey A. Gruzdkov
Published in: Nutrients, Issue 13/7, 2021, Page(s) 2474, ISSN 2072-6643
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/nu13072474

Network Diffusion Promotes the Integrative Analysis of Multiple Omics

Author(s): Noemi Di Nanni, Matteo Bersanelli, Luciano Milanesi, Ettore Mosca
Published in: Frontiers in Genetics, Issue 11, 2020, ISSN 1664-8021
Publisher: Frontiers Media
DOI: 10.3389/fgene.2020.00106

Analysis of Faecal Microbiota and Small ncRNAs in Autism: Detection of miRNAs and piRNAs with Possible Implications in Host-Gut Microbiota Cross-Talk

Author(s): Chiappori F., Cupaioli F.A., Consiglio A., Di Nanni N., Mosca E., Licciulli V.F., Mezzelani A.
Published in: Nutrients, Issue 14(7):1340, 2022 Mar 23, 2022, Page(s) 1-23, ISSN 2072-6643
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/nu14071340

The interaction between intestinal bacterial metabolites and phosphatase and tensin homolog in autism spectrum disorder

Author(s): Zheng Y, Prince N, van Hattem C, Garssen J, Pardo PP, Kraneveld AD
Published in: Molecular and Celullar Neuroscience, Issue Dec 30;124:103805, 2023, Page(s) 1-11, ISSN 1044-7431
Publisher: Academic Press
DOI: 10.1016/j.mcn.2022.103805

The role of bacterial-derived aromatic amino acids metabolites relevant in autism spectrum disorders: A comprehensive review

Author(s): Yuanpeng Zheng, Marie K Bek, Naika Z Prince, Lucia N Peralta Marzal, Johan Garssen, Paula Perez Pardo, Aletta D Kraneveld
Published in: Frontiers in Neuroscience, Issue October, 2021, Page(s) 1401, ISSN 1662-453X
Publisher: Frontiers
DOI: 10.3389/fnins.2021.738220

Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome–Host Interaction Mechanistic Hypothesis

Author(s): Athanasios Beopoulos, Manuel Gea, Alessio Fasano, François Iris
Published in: Nutrients, 2021, ISSN 2072-6643
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/nu14010065

Assessment of haptoglobin alleles in autism spectrum disorders

Author(s): Cupaioli FA, Mosca E, Magri C, Gennarelli M, Moscatelli M, Raggi ME, Landini M, Galluccio N, Villa L, Bonfanti A, Renieri A, Fallerini C, Minelli A, Marabotti A, Milanesi L, Fasano A, Mezzelani A
Published in: Scientific Reports, Issue 10(1):7758, 2020 May 8, 2020, Page(s) 1-11, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-64679-w

Lactobacillus salivarius and Lactobacillus gasseri supplementation reduces stress-induced sugar craving in mice

Author(s): Nicol M., Lahaye E., El Mehdi M., do Rego J.-L., do Rego J.-C., Fetissov S.O.
Published in: European Eating Disorders Review, 2023, ISSN 1099-0968
Publisher: Wiley
DOI: 10.1002/erv.3004

The Impact of Gut Microbiota-Derived Metabolites in Autism Spectrum Disorders

Author(s): Lucía N. Peralta-Marzal, Naika Prince, Djordje Bajic, Léa Roussin, Laurent Naudon, Sylvie Rabot, Johan Garssen, Aletta D. Kraneveld and Paula Perez-Pardo
Published in: International Journal of Molecular Sciences, Issue Volume 22, Issue 18, 2021, semimonthly, 2021, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms221810052

The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17

Author(s): Yuanpeng Zheng, Tessa A. Verhoeff, Paula Perez Pardo, Johan Garssen and Aletta D. Kraneveld
Published in: International Journal of Molecular Sciences, Issue volume 22, issue 1, 2021, semimonthly, 2021, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms22010118

The Autism Spectrum Disorder-Associated Bacterial Metabolite p-Cresol Derails the Neuroimmune Response of Microglial Cells Partially via Reduction of ADAM17 and ADAM10

Author(s): Zheng, Y.; Prince, N.Z.; Peralta Marzal, L.N.; Ahmed, S.; Garssen, J.; Perez Pardo, P.; Kraneveld, A.D.
Published in: Int J Mol Sci, Issue Sep 20;23(19):11013, 2022, Page(s) 1-17, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms231911013

Autism Spectrum Disorders: Analysis of Mobile Elements at 7q11.23 Williams–Beuren Region by Comparative Genomics

Author(s): Francesca Anna Cupaioli, Chiara Fallerini, Maria Antonietta Mencarelli, Valentina Perticaroli, Virginia Filippini, Francesca Mari, Alessandra Renieri, Alessandra Mezzelani
Published in: Genes, Issue 12/10, 2021, Page(s) 1605, ISSN 2073-4425
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/genes12101605

Characterization and comparison of gene-centered human interactomes

Author(s): Ettore Mosca, Matteo Bersanelli, Tommaso Matteuzzi, Noemi Di Nanni, Gastone Castellani, Luciano Milanesi, Daniel Remondini
Published in: Briefings in Bioinformatics, 2021, ISSN 1467-5463
Publisher: Oxford University Press
DOI: 10.1093/bib/bbab153

Protein extract of a probiotic strain Hafnia alvei and bacterial ClpB protein improve glucose tolerance in mice

Author(s): Zolotarev V.A., Murovets V.O., Sepp A.L., Sozontov E.A., Lukina E.A., Khropycheva R.P., Pestereva N.S., Ivleva I.S., El Mehdi M., Lahaye E., Chartrel N., Fetissov S.O.
Published in: International Journal of Molecular Sciences, Issue 24(13), 10590, 2023, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms241310590

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach

Author(s): Jacopo Troisi, Reija Autio, Thanos Beopoulos, Carmela Bravaccio, Federica Carraturo, Giulio Corrivetti, Stephen Cunningham, Samantha Devane, Daniele Fallin, Serguei Fetissov, Manuel Gea, Antonio Giorgi, François Iris, Lokesh Joshi, Sarah Kadzielski, Aletta Kraneveld, Himanshu Kumar, Christine Ladd-Acosta, Geraldine Leader, Arlene Mannion, Elise Maximin, Alessandra Mezzelani, Luciano Milanesi, Lau
Published in: Brain Sciences, Issue 10/10, 2020, Page(s) 743, ISSN 2076-3425
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/brainsci10100743

Gut Reactions: How Far Are We from Understanding and Manipulating the Microbiota Complexity and the Interaction with Its Host? Lessons from Autism Spectrum Disorder Studies

Author(s): Martina Lombardi, Jacopo Troisi
Published in: Nutrients, Issue 13/10, 2021, Page(s) 3492, ISSN 2072-6643
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/nu13103492

Change of Communication Strategy to Increase Engagement during the SARS-Cov-2Pandemic: The Experience of the European GEMMA Project in Italy

Author(s): Cupaioli Francesca Anna, Corrivetti Giulio, Tamburro Ilaria, Fasano Alessio, Mezzelani Alessandra
Published in: International Journal of Humanities, Social Sciences and Education, Issue 7/9, 2020, ISSN 2349-0381
Publisher: ARC Publications Pvt Ltd
DOI: 10.20431/2349-0381.0709013

Network-Based Integrative Analysis of Genomics, Epigenomics and Transcriptomics in Autism Spectrum Disorders

Author(s): Noemi Di Nanni, Matteo Bersanelli, Francesca Anna Cupaioli, Luciano Milanesi, Alessandra Mezzelani, Ettore Mosca
Published in: International Journal of Molecular Sciences, Issue 20/13, 2019, Page(s) 3363, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms20133363

Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence

Author(s): Léa Roussin, Naika Prince, Paula Perez-Pardo, Aletta D. Kraneveld, Sylvie Rabot, Laurent Naudon
Published in: Microorganisms, Issue 8/9, 2020, Page(s) 1369, ISSN 2076-2607
Publisher: MDPI
DOI: 10.3390/microorganisms8091369

Blood levels of neuropeptide 26RFa in relation to anxiety and aggressive behavior in humans - an exploratory study

Author(s): Værøy H., Takhlidjt S., Cherifi Y., Lahaye E., Chartrel N., Fetissov S.O.
Published in: Brain Sciences, Issue 13(2), 237, 2023, ISSN 2076-3425
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/brainsci13020237

Immunoglobulin G is a natural oxytocin carrier which modulates oxytocin receptor signaling - relevance to aggressive behavior in humans

Author(s): Værøy H., Lahaye E., Dubessy C., Benard M., Nicol M., Cherifi Y., Takhlidjt S., do Rego J.-L., do Rego J.-C., Chartrel N., Fetissov S.O.
Published in: Discover Mental Health, Issue Oct 19;3(1):21, 2023, Page(s) Volume 3, article number 21, ISSN 2731-4383
Publisher: Springer
DOI: 10.1007/s44192-023-00048-z

Autism spectrum disorders pathogenesis: Toward a comprehensive model based on neuroanatomic and neurodevelopment considerations

Author(s): Beopoulos A, Géa M, Fasano A, Iris F
Published in: Frontiers in neuroscience, Issue Nov 03 3;16:988735, 2022, Page(s) 1-24, ISSN 1662-453X
Publisher: Frontiers
DOI: 10.3389/fnins.2022.988735

Gene relevance based on multiple evidences in complex networks

Author(s): Noemi Di Nanni, Matteo Gnocchi, Marco Moscatelli, Luciano Milanesi, Ettore Mosca
Published in: Bioinformatics, 2019, ISSN 1367-4803
Publisher: Oxford University Press
DOI: 10.1093/bioinformatics/btz652

Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection

Author(s): Oommen A, Cunningham S, Joshi L.
Published in: Viruses, Issue Jan 8;13(1):82, 2021, Page(s) 1-15, ISSN 1999-4915
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/v13010082

Conference proceedings (3)

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study: Beyond biomarker identification for the precision treatment and early detection of autism spectrum disorders

Author(s): J. Troisi, M. Lombardi, SJK Symes, G. Scala, M. Delli Carri, SM Richards & GEMMA Consortium
Published in: Bioinformatics and Computational Biology Conference, 2022
Publisher: F1000 Research
DOI: 10.7490/f1000research.1119307.1

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study: Beyond the Biomarkers Identification for a Precision Treatment and Primary Prevention of Autism Spectrum Disorders

Author(s): SJK Symes, M Lombardi, G Scala, M Delli Carri, SM Richards, GEMMA Consortium, & J Troisi
Published in: 18th International Conference of the Metabolomics Society, 2022
Publisher: Metabolomics Society

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study: Beyond the Biomarkers Identification for a Precision Treatment and Primary Prevention of Autism Spectrum Disorders

Author(s): SJK Symes, M Lombardi, G Scala, M Delli Carri, SM Richards, GEMMA Consortium, & J Troisi
Published in: 4th Annual MANA (Metabolomics Association of North America), 2022
Publisher: Metabolomics Association of North America

Other (5)

Progress in the Puzzle Resolution: The Molecular Genetics Underpinning Autism Spectrum Disorders

Author(s): Mezzelani A, Cupaioli F.A.
Published in: Brain Science, Issue 2023 Dec 7;13(12):1688, 2023, ISSN 2076-3425
Publisher: MDPI
DOI: 10.3390/brainsci13121688

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Author(s): Brittany D. Needham, Mark D. Adame, Gloria Serena, Destanie R. Rose, Gregory M. Preston, Mary C. Conrad, A. Stewart Campbell, David H. Donabedian, Alessio Fasano, Paul Ashwood, Sarkis K. Mazmanian
Published in: Journal Biological Psychiatry, Issue Volume 89, Issue 5, 2021, Page(s) 451-462, ISSN 0006-3223
Publisher: Elsevier
DOI: 10.1016/j.biopsych.2020.09.025

Gut Microbiota-Brain Axis in Regulation of Feeding Behavior

Author(s): Fetissov SO
Published in: Microorganisms, Issue 11(3), 749, 2023, ISSN 2076-2607
Publisher: MDPI
DOI: 10.3390/microorganisms11030749

Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis

Author(s): Asbjornsdottir, B.; Snorradottir, H.; Andresdottir, E.; Fasano, A.; Lauth, B.; Gudmundsson, L.S.; Gottfredsson, M.; Halldorsson, T.I.; Birgisdottir, B.E.
Published in: Nutrients, Issue Jul 3;12(7):1982, 2020, Page(s) 1-27, ISSN 2072-6643
Publisher: MDPI
DOI: 10.3390/nu12071982

Optimization of Peripheral Blood Mononuclear Cell Extraction from Small Volume of Blood Samples: Potential Implications for Children-Related Diseases

Author(s): Patrone, D.; Alessio, N.; Antonucci, N.; Brigida, A.L.; Peluso, G.; Galderisi, U.; Siniscalco, D.
Published in: Journal Methods Protoc, Issue Feb 24;5(2):20, 2022, Page(s) 1-6, ISSN 2409-9279
Publisher: MDPI
DOI: 10.3390/mps5020020