Depression is a mental disorder that affects
more than 264 million people of all ages worldwide. Understanding its
mechanisms is vital for the development of effective therapeutic
strategies. Scientists from the Institut Pasteur, Inserm and the CNRS
recently conducted a study showing that an imbalance in the gut
bacterial community can cause a reduction in some metabolites, resulting
in depressive-like behaviors. These findings, which show that a healthy
gut microbiota contributes to normal brain function, were published in Nature Communications on December 11, 2020.
The bacterial population in the gut, known as the gut microbiota, is
the largest reservoir of bacteria in the body. Research has increasingly
shown that the host and the gut microbiota are an excellent example of
systems with mutually beneficial interactions. Recent observations also
revealed a link between mood disorders and damage to the gut microbiota.
This was demonstrated by a consortium of scientists from the Institut
Pasteur, the 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, scientists recently discovered that a change to
the gut microbiota brought about by chronic stress can lead to
depressive-like behaviors, 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. Gut
microbiota plays a role in brain function and mood regulation
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 behaviors.
The scientists obtained these results by studying the microbiotas of
healthy animals and animals with mood disorders. As Pierre-Marie Lledo,
Head of the Perception and Memory Unit at the Institut Pasteur
(CNRS/Institut Pasteur) and joint last author of the study, explains:
"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 behaviors in the latter."
The scientists 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 behaviors. These bacteria could therefore serve as an
antidepressant. Such treatments are known as "psychobiotics."
"This discovery shows the role played by the gut microbiota in normal
brain function," continues GĂ©rard Eberl, Head of the Microenvironment
and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the
study. If there is an imbalance in the gut bacterial community, some
lipids that are vital for brain function disappear, encouraging the
emergence of depressive-like behaviors. In this particular case, the use
of specific bacteria could be a promising method for restoring a
healthy microbiota and treating mood disorders more effectively.