gut microbiota

Role of the gut microbiota in the development of alcohol use disorder

The gut microbiota is composed of a very large number of bacteria, viruses, fungi and yeasts that play an important role in the body, through the production of a series of metabolites (including neurotransmitters), and through an essential role in the barrier function of the gut and the regulation of immunity and stress response. In this lecture I will present, based mainly on human studies but also on preclinical studies, the evidence for a role of the gut microbiota in the development of alcohol use disorder. I will show the first results of trials to test the effects of nutritional approaches to address these deficits.

How much gut needs the brain ? Gut microbiota-immune crosstalk in neuroinflammation

Microbiome and behaviour: Exploring underlying mechanisms

Environmental insults alter brain function and behaviour inboth rodents and people. One putative underlying mechanism that has receivedsubstantial attention recently is the gut microbiota, the ecosystem ofsymbiotic microorganisms that populate the intestinal tract, which is known toplay a role in brain health and function via the gut-brain axis. Two keyenvironmental insults known to affect both brain function and behaviour, andthe gut microbiome, are poor diet and psychological stress. While there isstrong evidence for interactions between the microbiome and host physiology inthe context of chronic stress, little is known about the role of the microbiomein the host response to acute stress. Determining the underlying mechanisms bywhich stress may provoke functional changes in the gut and brain is criticalfor developing therapeutics to alleviate adverse consequences of traumaticstress.

Gut Feelings: The Microbiota-Gut-Brain Axis Across the Lifespan

The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour during early life, adolescence & ageing. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics. Recently, the gut microbiota has been implicated in regulating the stress response, and social behaviour. Moreover, fundamental brain processes from adult hippocampal neurogenesis to myelination to microglia activation have been shown to be regulated by the microbiome. Further studies will focus on understanding the mechanisms underlying such brain effects and how they can be exploited by microbiota-targeted interventions including ‘psychobiotics’ and diet

New Strategies and Approaches to Tackle and Understand Neurological Disorder

Broadly, the Mauro Costa-Mattioli laboratory (The MCM Lab) encompasses two complementary lines of research. The first one, more traditional but very important, aims at unraveling the molecular mechanisms underlying memory formation (e.g., using state-of-the-art molecular and cell-specific genetic approaches). Learning and memory disorders can strike the brain during development (e.g., Autism Spectrum Disorders and Down Syndrome), as well as during adulthood (e.g., Alzheimer’s disease). We are interested in understanding the specific circuits and molecular pathways that are primarily targeted in these disorders and how they can be restored. To tackle these questions, we use a multidisciplinary, convergent and cross-species approach that combines mouse and fly genetics, molecular biology, electrophysiology, stem cell biology, optogenetics and behavioral techniques. The second line of research, more recent and relatively unexplored, is focused on understanding how gut microbes control CNS driven-behavior and brain function. Our recent discoveries, that microbes in the gut could modulate brain function and behavior in a very powerful way, have added a whole new dimension to the classic view of how complex behaviors are controlled. The unexpected findings have opened new avenues of study for us and are currently driving my lab to answer a host of new and very interesting questions: - What are the gut microbes (and metabolites) that regulate CNS-driven behaviors? Would it be possible to develop an unbiased screening method to identify specific microbes that regulate different behaviors? - If this is the case, can we identify how members of the gut microbiome (and their metabolites) mechanistically influence brain function? - What is the communication channel between the gut microbiota and the brain? Do different gut microbes use different ways to interact with the brain? - Could disruption of the gut microbial ecology cause neurodevelopmental dysfunction? If so, what is the impact of disruption in young and adult animals? - More importantly, could specific restoration of selected bacterial strains (new generation probiotics) represent a novel therapeutic approach for the targeted treatment of neurodevelopmental disorders? - Finally, can we develop microbiota-directed therapeutic foods to repair brain dysfunction in a variety of neurological disorders?

Interactions between the microbiome and nervous system during early development

The gut microbiota is emerging as an important modulator of brain function and behavior, as several recent discoveries reveal substantial effects of the microbiome on neurophysiology, neuroimmunity and animal behavior. Despite these findings supporting a “microbiome-gut-brain axis”, the molecular and cellular mechanisms that underlie interactions between the gut microbiota and brain remain poorly understood. To uncover these, the Hsiao laboratory is mining the human microbiota for microbial modulators of host neuroactive molecules, investigating the impact of microbiota-immune system interactions on neurodevelopment and examining the microbiome as an interface between gene-environment interactions in neurological diseases. In particular, our research on effects of the maternal microbiome on offspring development in utero are revealing novel interactions between microbiome-dependent metabolites and fetal thalamocortical axonogenesis. Overall, we aim to dissect biological pathways for communication between the gut microbiota and nervous system, toward understanding fundamental interactions between physiological systems that impact brain and behavior.

Effects of early-life sodium butyrate supplementation on autism-like behavioral phenotype, neuroinflammatory profile and gut microbiota alterations induced by maternal immune activation in mouse offspring

Depression-Induced Early Onset of Alzheimer’s Disease is Associated with Gut Microbiota in Mice

Effect of gut microbiota from children with autism spectrum disorder on behavior and ASD-related biological markers in germ-free mice

Impact of the gut microbiota on nicotine effects and glia within the reward system in mice

Gut microbiota from autistic children induce changes in the central nervous system of healthy mice

Gut microbiota – hippocampus synergisms in non-clinical subjects with high positive schizotypy

The gut microbiota regulates the catecholamine biosynthetic pathway in the adrenal glands of stressed rats

Modulation of gut microbiota by antibiotics did not affect anhedonia in a high-fat diet-induced model of depression in male mice

Social isolation in adolescence: changes in the gut microbiota composition and in the hippocampal inflammation

Targeting the gut microbiota for possible biomarkers in Alzheimer’s disease

AAV-mediated overexpression of wild-type human alpha-synuclein leads to alterations in gut microbiota in a ‘brain-first’ rat model of prodromal Parkinson’s disease

FENS Forum 2024

Extracellular vesicles from mesenchymal stem cells alter gut microbiota and improve neuroinflammation and motor impairment in rats with mild liver damage

FENS Forum 2024

The maternal gut microbiota regulates embryonic cortical development in mice

FENS Forum 2024

Gut microbiota alterations and hypothalamic inflammation precede obesity in a rat model of binge eating

FENS Forum 2024

A novel sEH inhibitor reduces inflammation and promotes neuroprotective effects by modulating gut microbiota

FENS Forum 2024

The pesticide glyphosate induces sex-dependent behavioural changes in mice: A role for the gut microbiota?

FENS Forum 2024

Primary sensory neurons require a functional interleukin-6 signal transducer to regulate gut microbiota composition in mice

FENS Forum 2024

Targeting the gut microbiota to ameliorate the effects of an early-life high-fat/high-sugar diet on eating behaviour in adolescence and adulthood

FENS Forum 2024