Gut microbiota's role in brain function and mood regulation
French scientists have found that an imbalance in the gut bacterial community can cause a reduction in some metabolites, resulting in depressive-like behaviours. Published in the journal Nature Communications, their findings indicate that a healthy gut microbiota contributes to normal brain function.
Recent observations have revealed a link between mood disorders and damage to the bacterial population in the gut, known as the gut microbiota. This was demonstrated by a consortium of scientists from the Institut Pasteur, the Centre national de la recherche scientifique (CNRS) and Inserm, who identified a correlation between the gut microbiota and the efficacy of fluoxetine — a molecule frequently used as an antidepressant. But some of the mechanisms governing depression, the leading cause of disability worldwide, remained unknown.
Using animal models, the scientists discovered that a change to the gut microbiota brought about by chronic stress can lead to depressive-like behaviours, in particular by causing a reduction in lipid metabolites (small molecules resulting from metabolism) in the blood and the brain. These lipid metabolites, known as endogenous cannabinoids (or endocannabinoids), coordinate a communication system in the body which is significantly hindered by the reduction in metabolites.
Endocannabinoids bind to receptors that are also the main target of THC, the most widely known active component of cannabis. The scientists discovered that an absence of endocannabinoids in the hippocampus, a key brain region involved in the formation of memories and emotions, resulted in depressive-like behaviours. They obtained these results by studying the microbiotas of healthy animals and animals with mood disorders.
The scientists also identified some bacterial species that are significantly reduced in animals with mood disorders. They then demonstrated that an oral treatment with the same bacteria restored normal levels of lipid derivatives, thereby alleviating the depressive-like behaviours. These bacteria could therefore serve as an antidepressant.
“Surprisingly, simply transferring the microbiota from an animal with mood disorders to an animal in good health was enough to bring about biochemical changes and confer depressive-like behaviours in the latter,” said Pierre-Marie Lledo, Head of the Perception and Memory Unit at the Institut Pasteur and joint last author of the study.
The research therefore shows the role played by the gut microbiota in normal brain function, and how specific bacteria could be used for restoring a healthy microbiota and treating mood disorders more effectively.
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