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 Gérard 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.
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