Imbalance in the gut bacterial community can result in depressive-like behaviors

Gut microbiota plays a role in brain function and mood regulation.


Depression is the leading cause of disability worldwide, currently affecting more than 264 million people.

Regardless of the prevalence of depression and its economic effect, its pathophysiology keeps on being exceptionally discussed. A superior comprehension of the mechanism prompting depression is essential for developing effective therapeutic strategies.

A new study by the Institut Pasteur, Inserm, and the CNRS has found that an imbalance in the gut microbiota’s bacterial population, known as the gut microbiota, can significantly reduce some metabolites, triggering depressive-like behaviors. The study indicates a healthy gut microbiota contributes to normal brain function.

Recently, a consortium of scientists from the Institut Pasteur, the CNRS, and Inserm identified a relationship between mood disorders and damage to the gut microbiota.

In this new study conducted on animal models, scientists discovered that chronic stress could cause changes to the gut microbiota, leading to depressive-like behaviors. This reduces lipid metabolites (small molecules resulting from metabolism) in the blood and the brain. These lipid metabolites, known as endogenous cannabinoids (or endocannabinoids), a coordinate communication system in the body that is altogether obstructed by the reduction in metabolites.

The absence of endocannabinoids in the hippocampus triggers depressive-like behaviors.

Scientists studied the microbiotas of healthy animals and animals with mood disorders.

They identified some bacterial species that are significantly reduced in animals with mood disorders. They then demonstrated that oral treatment with the same bacteria restored normal lipid derivatives levels, thereby alleviating the depressive-like behaviors. These bacteria could, therefore, serve as an antidepressant. Such treatments are known as “Psychobiotics.”

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.”

Gérard Eberl, Head of the Microenvironment and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the study, said, “This discovery shows the role played by the gut microbiota in normal brain function. 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.”

Journal Reference:
  1. Chevalier, G., Siopi, E., Guenin-Macé, L. et al. Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system. Nat Commun 11, 6363 (2020). DOI: 10.1038/s41467-020-19931-2
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