Project description
Trafficking mechanisms and sex-biased effects of gut microbial products on the brain
The microbiota-gut-brain axis, a bidirectional network linking the intestinal bacteria and the central nervous system, influences intestinal functions, mental health and beyond. Funded by the European Research Council, the MicrobiotaNeuroTalk project focuses on the direct effects of components of the peptidoglycan layer of bacterial cell walls known as muropeptides on brain neurons. This interdisciplinary research will investigate the transport mechanisms and the physiological factors, such as hormones, that influence the interactions of muropeptides with brain neuronal cells, shedding light on the regulation and sex-biased impacts of microbial products in the brain. Insights could revolutionise neurological disorder therapies that have a different impact on men and women and that are influenced by microbiota, such as Alzheimer's and Parkinson's diseases.
Objective
The gut-brain axis has emerged as a complex regulator of system-wide physiology, playing essential roles to maintain homeostasis, including contributions to brain development and activity, affecting host metabolism and behavior. The gut bacterial composition constantly fluctuates, allowing for the regular release of diverse microbe-derived compounds into the bloodstream. Although it is known that many gut-bacterial metabolites affect distant organs such as the brain, their direct interaction with brain neurons is rarely demonstrated. The impact of microbial metabolites on brain mechanisms are generally thought to be indirect due to interaction with, for example, the immune system or the vagus nerve. However, my previous work has shown that microbe-derived muropeptides reach the brain and decrease the spontaneous activity of brain neurons that express the Nod2 receptor. Remarkably, this direct interaction affected appetite and thermoregulation in a sex- and age-dependent fashion. Nevertheless, to further understand these direct interactions, some questions still need to be addressed: how does this compound reach the brain? Which factors may lead to this sex- and age-dependent neuronal activation? Are there other neuroactive bacterial compounds directly affecting brain neurons? Therefore, using interdisciplinary approaches, I propose to (1) unravel gut-brain trafficking mechanisms, (2) define physiological factors (e.g. hormones) that shape this microbe-neuron interaction and (3) describe new bacterial compounds that affect hypothalamic circuits and their downstream effects. This proposal will expose novel aspects of host-microbe interactions, leading to a more complete and integrated understanding of bacterial influence on host’s essential functions. It may also lead to new therapeutic approaches for neurological disorders that exhibit specific sex prevalence and where the microbiota is a factor in disease susceptibility, such as Alzheimer’s and Parkinson’s diseases.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesbasic medicineneurologyparkinson
- medical and health sciencesbasic medicinephysiologyhomeostasis
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
1067-001 LISBOA
Portugal