"A healthy mind... with a healthy microbiota." These words sum up a recent study demonstrating the close link between the composition of the gut microbiota and depressive disorders. In the same paper, the scientists also offered proof that direct communication between the gut microbiota and the brain requires the vagus nerve, paving the way for therapeutic solutions.
The adult human body is composed of 100,000 billion cells. It also interacts closely with a roughly equal number of microbes – bacteria, viruses or fungi. This microbial community, known as the microbiota, plays a key role in several essential biological processes including immunity and metabolism.
Over the past few years, scientists have been looking more specifically at the gut microbiota and its composition. Investigating the gut microbiota can improve our understanding of its implications for human health. Recently, for example, a link was established between the gut microbiota and certain inflammatory reactions. Previously, a direct dialog between the gut microbiota and the brain, associated with metabolic disorders such as diabetes and obesity, had also been demonstrated.
In a joint study conducted by the Institut Pasteur, the CNRS and Inserm, scientists used an animal model to demonstrate another strong link between the brain and the gut microbiota. The scientists observed that transferring the microbiota of stressed mice to healthy mice produced characteristic depressive-like behavior in the healthy mice: less motivation, a loss of pleasure and apathy.
Direct communication between the gut microbiota and the brain via the vagus nerve
The scientists did not stop at this observation and took their study further, sketching out a possible therapeutic approach. They also performed a vagotomy – in other words the surgical removal of part of the vagus nerve in the abdomen – on the mice who had just received the microbiota from stressed mice. The results showed that these mice with a newly imbalanced gut microbiota did not exhibit depressive-like behavior. "We showed that decoupling the gut and the brain by vagotomy protected the subject from the depressive-like behavior produced by gut dysbiosis," explains Pierre-Marie Lledo, CNRS Director of Research and Head of the Institut Pasteur's Perception and Memory Unit.
By showing how vagotomy can protect against certain forms of depression, this study conducted in animals may pave the way for alternative therapeutic strategies to relieve depression in the 30% of people who experience no benefits from antidepressant treatment. The theory now needs to be tested and the research results confirmed in humans.
This study comes under the Brain connectivity and neurodegenerative diseases priority scientific area as part of the Institut Pasteur's 2019-2023 Strategic Plan.
This research received funding from AG2R La Mondiale.
Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice, Molecular Psychiatry, May 2, 2023
Eleni Siopi1,2, Mathieu Galerne2,4, Manon Rivagorda2,4, Soham Saha1, Carine Moigneu1, Stéphanie Moriceau3, Mathilde Bigot1, Franck Oury2,5 and Pierre-Marie Lledo1,5
1Institut Pasteur, Université Paris Cité, CNRS UMR 3571, Perception and Memory Unit, 75015 Paris, France.
2Université Paris Cité, CNRS, INSERM, Institut Necker Enfants Malades-INEM, 75015 Paris, France.
3Platform for Neurobehavior and Metabolism, Structure Fédérative de Recherche Necker, 26 INSERM US24/CNRS UAR 3633, 75015 Paris, France.
4These authors contributed equally: Mathieu Galerne, Manon Rivagorda.
5These authors jointly supervised this work: Franck Oury, Pierre-Marie Lledo.