The Gut Microbiome in Neuroinflammation and Neurodevelopmental Disorders – µNeuroINF

The brain is an extraordinarily complex organ that develops early on in embryonic life.
Neurodevelopment results from the execution of epigenetic and genetic programs, and is strongly
influenced by environmental factors. A precise sequence of events is initiated, which, while disrupted
by genetic defects or environmental insults such as infections, provokes non-recoverable
developmental alterations leading to mental diseases. In addition to the synaptic and/or connectivity
dysfunctions associated to neurodevelopmental disorders, inflammation in the brain (otherwise called
neuroinflammation) is one of the hallmarks shared by different neurodevelopmental disorders, such as
Down syndrome, Fragile X syndrome and Autism Spectrum Disorders. In fact, neuroinflammation
drastically affects brain activity and behaviour. Recent studies demonstrate the existence of a gutbrain
axis through which the intestinal microbiota is able to modulate inflammation and impact
behaviour. The µNeuroINF project will explore the hypothesis that our gut bacteria may trigger
neuroinflammation, which in turn impacts metabolism and behaviour, and ultimately contributes to
neurodevelopmental disease progression. Using mouse models of Down syndrome, Fragile X
syndrome and autism spectrum disorders, we will study the gut bacteria, their genes, proteins and
metabolites to identify which microbial metabolites common to these diseases are absorbed in the gut
and diffuse into the bloodstream to reach the brain. The potential pro-inflammatory role of these
metabolites will be investigated in vitro by screening their pharmacological targets in the host, and in
vivo in the animal models of the disease. This will ultimately lead to novel therapeutic strategies for
NDD driven by the gut microbiome. The µNeuroINF initiative is an innovative multidisciplinary project
targeting the role of the gut bacteria in neuroinflammation. Our unique research strategy uses cuttingedge
technologies to explore how gut microbes modulate brain inflammation in neurodevelopmental
disorders. Not only the project will demonstrate one of the most fundamental mechanisms by which
our gut bacteria influence our behaviour, but it will also identify the microbial metabolites that can be
used to better monitor brain inflammation (“biomarkers”) or to lead to new drugs (“lead compounds”)
for the treatment of neuroinflammation.