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Gemma CONFERENCES

Table of Contents

21st Annual Meeting of the Bioinformatics Italian Society (BITS), June 11-13, 2025, Naples, Italy

Understanding how the human body interacts with gut microbes is important for studying complex conditions like autism. We created a new molecular map, or “interactome” for the analysis of host-microbiota multi-omics data, that includes not just human genes but also microbial genes and other biological factors. We tested this tool using data from people with autism and found it could identify key biological pathways, especially those related to the metabolism of amino acids involved in biosynthesis of neurotransmitters. It also showed some ability to distinguish between people with and without autism. These early results match findings from recent research and suggest this new tool could help uncover important insights from complex biological data.
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Neurogenomics Conference, Milan (IT), May 19-21, 2025

By comparing genes related to social behavior across species, researchers identified a network of human genes strongly linked to autism. Many of these genes are involved in brain development and communication between cells. This cross-species approach may help discover new autism-related genes and improve our understanding of human social behavior.
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International Human Microbiome Consortium (IHMC) 2024, June 22-25, Rome

Previous studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism. Alterations in circulating 5-HT levels and gut 5-HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5-HT metabolism in the brain and along the GI tract of GF male mice compared to conventional (CV) ones. We found a strong decrease in locomotor activity, accompanied by some signs of increased anxiety-like behavior in GF mice compared with CV mice. Brain gene expression analysis showed no differences in HTR1A and TPH2 genes. In the gut, we found decreased TPH1 expression in the colon of GF mice, while it was increased in the cecum. HTR1A expression was dramatically decreased in the colon, while HTR4 expression was increased both in the cecum and colon of GF mice compared to CV mice. Finally, SLC6A4 expression was increased in the ileum and colon of GF mice compared to CV mice. Our results add to the evidence that the microbiota is involved in regulation of behavior, although heterogeneity among studies suggests a strong impact of genetic and environmental factors on this microbiota-mediated regulation. While no impact of GF status on brain 5-HT was observed, substantial differences in gut 5-HT metabolism were noted, with tissue-dependent results indicating a varying role of microbiota along the GI tract. 

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Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition characterized by repetitive behaviours and impairments in social interaction and communication, often coexisting with anxiety, cognitive deficits, and gastrointestinal (GI) symptoms. Altered gut microbiota composition has been observed in individuals with ASD and murine models of ASD. Such microbiota alterations may exacerbate symptoms of ASD, as they can impact the immune system, contributing to dysregulated serotonin and kynurenine pathways, and increased neuroinflammation. This study evaluates the impact of human faecal microbiota transplantation (hFMT) from children with ASD and GI symptoms or from their neurotypical siblings to two strains of germ-free (GF) mice, focusing on autism-related behaviours, kynurenine and serotonin metabolism and immune parameters.

Results highlights:

  • hFMT from ASD and GI donors or neurotypical siblings led to distinct microbiota profiles
  • hFMT led to impaired behaviour in recipients from the ASD and GI symptoms group
  • hFMT also impacted inflammatory T cell profiles and kynurenine metabolism
  • Mouse genetic background influenced the outcomes of hFMT
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Autism Spectrum Disorder (ASD) affects about 1 in 54 children in the U.S.A., with a significant increase since 1960. While improved awareness and clinical practices may explain some of this rise, they do not fully account for it. Research suggests a link between ASD and gut microbiota due to gastrointestinal issues in many affected children. Current studies are limited in understanding the mechanisms of ASD. The GEMMA study, supported by the European Commission, aims to follow at-risk infants (because they are siblings of autistic children) from birth to identify biomarkers for ASD development, involving both clinical trials and pre-clinical studies to explore microbiome associations and potential treatment responses.
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Short chain fatty acids (SCFAs) are key gut microbial metabolites produced through microbial fermentation of dietary fibers in the colon. SCFAs are crucial for regulating intestinal inflammation, maintaining of mucosal barrier and facilitating gut-brain-interaction, all processes implicated in ASD pathophysiology. The aim of the study was to identify potential metabolic patterns associated with the onset and progression of ASD by longitudinal analysis (6, 12, 18, 24, 36 months) of fecal SCFAs level in individuals at risk of developing autism. A significant difference in the longitudinal development of certain SCFA profiles was found between children with and without ASD. This difference was most notable in acetic acid, hexanoic acid, hydroxybutyric acid and valeric acid. These differences indicate a possible role of the gut microbiome in the onset and progression of ASD may be because of changing in microbial composition or in the microbial metabolic activity within the gut environment of children with ASD
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The aim of this study was to unravel the fecal metabolomic landscape of autism spectrum disorders (ASD) through a longitudinal metabolomic analysis. Fecal samples were longitudinally collected from 38 children with autism and 32 neurotypical controls at different time points: 6, 12, 18, 24 months. Metabolome was extracted by MetaboPrep GC kit and analyzed by Gas Chromatography Mass-Spectrometry using GCMS-2010SE. Data were analyzed by MetaboPredict software and the class separation at different time points was explored using the Partial Least Square Discriminant Analysis (PLS-DA). The main significant difference between the two groups emerged at 18 months. Over time, this difference undergoes a significant reduction in variability within the ASD group compared to the control group.
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European Society of Human Genetics (ESHG) Conference, Berlin, June 1–4, 2024

The aim of this study was to identify a distinctive metabolomic pattern of the gut microbiota of the ASD condition and then to understand the altered pathways for early diagnosis, prognosis and future treatement. To this purpose we analyzed the metabolome of fecal samples of 40 children with ASD and 32 neurotipical children. Statistical analyses demonstrated a good separation between the two groups and found the metabolites with the highest degree of training: lactose, maltitol, maltose, mannobiose, estradiol, cellobiose, ribose, arabinose, asparagine, gluconic acid. The pathways most involved were those of lactose degradation and lactose synthesis. These findings pave the way for potential therapeutic intervention targeting the gut microbiota.gy.

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Molecular network analysis of the cross-talk between genetics, brain gene activity and gut microbiota in autism spectrum disorder​

Autism Spectrum Disorders (ASD) may be influenced by the gut microbiota, but the connection between the gut and the brain is complex and requires different levels of analysis. In this study, we used network analysis to better understand how genes linked to ASD, brain function, and gut microbes are connected. We focused on genes altered by ASD-related genetic factors, brain gene activity, and the gut microbiota. The resulting gene network showed strong interconnections between gut and brain, highlighting microbial genes that affect the metabolism of amino acids important for neurotransmitter production. This supports the idea that the microbiome could influence brain function through metabolic pathways.
This study was presented at different conferences:

  • International Human Microbiome Consortium (IHMC) 2024, June 22-25, Rome; BBMRI conference
  • 09/07/2024 – Annual Meeting Strengthening BBMRI.it
  • International Scientific association for Probiotics and Prebiotics (ISAPP) annual meeting, July 9-11, 2024, Cork
  • European Pediatric Translational Research Infrastructure (EPTRI) Scientific Meeting, 18 and 19 of July, Bari, Italy

Mind, Mood and Microbes, Amsterdam, the Netherlands, 10-11 May 2023

The GEMMA project (Genome, Environment, Microbiome and Metabolome in Autism) is a prospective study financed by the European Commission, which aims to identify potential biomarkers for personalized treatments and primary prevention of autism spectrum condition (ASC). The project includes preclinical studies consisting of faecal microbiota transplantations (FMT) from children with ASC to different mouse models to explore the contribution of the microbiota-gut-brain axis in the development or severity of ASC. Here, we present the results obtained in germ-free mice colonized with the faecal microbiota of a group of four children with ASC and suffering from gastro-intestinal disorders (chronic constipation). These mice were compared with their counterparts colonized with the faecal microbiota of the ASC donors’ neurotypical siblings. Characteristics of the faecal microbiota, namely alpha-diversity, beta-diversity, relative proportions of several bacterial phyla and families, and short-chain fatty acid profiles, differed between the two groups of mice. These differences in microbiota were accompanied by differences in gut biomarkers, suggesting increased inflammation and paracellular permeability in the ileum of mice associated with the faecal microbiota of the children with ASC. Finally, study of the behavioural phenotype showed that these mice had increased repetitive behaviour and impaired spatial memory, compared to their counterparts associated with the faecal microbiota of the neurotypical siblings. Future experiments will explore the possibility of mitigating these behavioural impairments through dietary intervention with synbiotics.

“Young researcher symposia” of FHU PaCeMM, Paris, France, 15 December 2022

The involvement of the microbiota-gut-brain axis has recently been taken into account in the study of the pathophysiology of autism spectrum disorders (ASD). Preclinical studies have shown that interventions on the gut microbiota, such as probiotic treatments or microbiota transplantations, can modulate behavior in animal models of ASD. The germ-free mouse is a potential model, as it shows impairments in social behavior and increased repetitive behaviors compared to conventional mice. Therefore, our project aimed to test the effect of fecal transplantation from children with ASD on behavior and several biological markers in germ-free mice. We hypothesized that behavioral phenotypes impaired in germ-free mice would not be improved, or even be worsened, by fecal microbiota from children with ASD , with or without gastro-intestinal (GI) symptoms as a co-morbidity (two distinct “ASD” groups) compared with mice receiving the microbiota from their neurotypical siblings (two distinct “Siblings” groups). We chose to perform the same experiment on two strains of mice : BALB/c and C57BL/6, as they show distinct emotivity levels, and have analyzed ASD related behaviors in the transplanted animals (i.e social behavior, repetitive behavior, anxiety and cognition (spatial memory). In addition, we are analyzing microbiota composition and fermentation activity, as well as markers of inflammation, permeability and the serotoninergic system.

Transplantation of fecal microbiota from children with ASD into both strains of mice was not accompanied by behavioral changes, with the exception of alterations in spatial memory in C57BL/6. Despite this, the composition of the microbiota that implanted into our four groups of BALB/c mice was distinct between groups, both in diversity and composition, with differences up to the Phylum level. Plus, short chain fatty acid profile also differed between groups indicating a difference of fermentation activity of the microbiota. The differences in the microbiota are accompanied by a reduction of the number of serotoninergic neurons in the raphe nuclei and of serotonin positive cells in the ileum in both “ASD” groups compared to their respective “Siblings” groups.  For C57BL/6 mice, these analyses are currently ongoing.

These preliminary results show that the microbiota of children with ASD, can cause some behavioral and biochemical differences in germ-free recipient mice. The current stage of our study is to complete all ongoing analyses and determine whether correlations exist between those differences and the microbial composition and activity of the transferred microbiota. 

Beneficial microbes conference (9th edition), Amsterdam, The Netherlands, 14-16 November 2022

The involvement of the microbiota-gut-brain axis has recently been taken into account in the study of the pathophysiology of autism spectrum disorders (ASD). Preclinical studies have shown that interventions on the gut microbiota, such as probiotic treatments or microbiota transplantations, can modulate behavior in animal models of ASD. The germ-free mouse is a potential model, as it shows impairments in social behavior and increased repetitive behaviors compared to conventional mice. Therefore, our project aimed to test the effect of fecal transplantation from children with ASD on behavior and several biological markers in germ-free mice. We hypothesized that behavioral phenotypes impaired in germ-free mice would not be improved, or even be worsened, by fecal microbiota from children with ASD , with or without gastro-intestinal (GI) symptoms as a co-morbidity (two distinct “ASD” groups) compared with mice receiving the microbiota from their neurotypical siblings (two distinct “Siblings” groups). We chose to perform the same experiment on two strains of mice : BALB/c and C57BL/6, as they show distinct emotivity levels, and have analyzed ASD related behaviors in the transplanted animals (i.e social behavior, repetitive behavior, anxiety and cognition (spatial memory). In addition, we are analyzing microbiota composition and fermentation activity, as well as markers of inflammation, permeability and the serotoninergic system.
Transplantation of fecal microbiota from children with ASD into both strains of mice was not accompanied by behavioral changes, with the exception of alterations in spatial memory in C57BL/6. Despite this, the composition of the microbiota that implanted into our four groups of BALB/c mice was distinct between groups, both in diversity and composition, with differences up to the Phylum level. Plus, short chain fatty acid profile also differed between groups indicating a difference of fermentation activity of the microbiota. The differences in the microbiota are accompanied by a reduction of the number of serotoninergic neurons in the raphe nuclei and of serotonin positive cells in the ileum in both “ASD” groups compared to their respective “Siblings” groups.  For C57BL/6 mice, these analyses are currently ongoing.
These preliminary results show that the microbiota of children with ASD, can cause some behavioral and biochemical differences in germ-free recipient mice. The current stage of our study is to complete all ongoing analyses and determine whether correlations exist between those differences and the microbial composition and activity of the transferred microbiota.

FENS Forum 2022, Paris, France, 9-13 July 2022

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacteria metabolites. This project aims to determine if the microbiota can influence behavior when transplanted to germ-free mice. Our hypothesis is that a pool of microbiota from patients with ASD, especially those with GI symptoms, will worsen behavioral phenotypes related to ASD in those mice as well as impact various ASD related biological markers, in comparison to GF mice transplanted with microbiota for the neurotypical siblings of those children. To ensure that the mice were exclusively exposed to donor microbiota, they were kept in isolators for the duration of the experiments. Experiments have been carried out on both BALB/c and C57BL/6 mice, but some analyses are still ongoing. 

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