Alzheimer's, Parkinson's, depression... Does the microbiota play a role in brain diseases?

“Brain diseases are among those where we are making the least progress in terms of treatments even though their number is increasing sharply,” regrets neuroscientist Pierre-Marie Lledo from the premises of the Pasteur Institute. There is currently no treatment that can cure Parkinson's or Alzheimer's disease. For depression, one in three people are resistant to antidepressants. “For a long time, we thought that everything happened in the brain. But the origin of the diseases perhaps comes from elsewhere, from an organ which would begin to fail years earlier,” continues the director of the Neuroscience department.

On the occasion of the 20th anniversary of Pasteurdon, the head of the Perception and Action unit of the Pasteur Institute opened the doors of his Parisian research laboratory to us. In these large brick buildings, scientists work in particular on the link between microbiota and brain diseases. “You’re going to see sliced ​​brains, enjoy your meal!” », warns, laughing, Doctor Lledo. Next to XXL microscopes, on the screens, fluorescent neurons in 3D.

Cognitive decline linked to intestinal bacteria

To understand whether the intestinal microbiota can influence age-related cognitive decline, a team from the laboratory carried out a study using two groups of young mice. The former were transplanted with microbiota from healthy elderly people and the latter with microbiota from elderly people suffering from Alzheimer's disease. Result: if in the first group, memory deteriorates in eight weeks, in the second, it deteriorates in just three weeks.

“We can compare the number of neurons in a healthy sample compared to a sick sample that has a memory problem, it’s completely brilliant,” says doctoral student Venera Khachatryan, zooming in on the 3D red brain displayed on her computer screen. We can really see all the neurons one by one. » At his side, the director of the Neuroscience department Pierre-Marie Lledo is pleased: “We were able to highlight some intestinal bacteria which contribute to premature aging and cognitive decline. »

The nasal microbiota

However, nothing proves in the current state of their research that these bacteria alone give rise to Alzheimer's disease in humans. A company supported by the Pasteur Institute was created in Montpellier to continue research and ultimately develop a drug aimed at slowing the decline of memory.

The intestines are not the only organs that are the subject of growing interest. Another team from the laboratory, led by Françoise Lazarini, is working on the involvement of the nasal microbiota in Parkinson's disease. Their result is just as promising: if the transfer of nasal flora from healthy mice to sick mice produces no effect, that from sick mice to healthy mice leads to the development of symptoms of Parkinson's disease.

Making antidepressants more effective

“We have identified around ten bacterial families likely to play a role,” says Pierre-Marie Lledo. This does not mean, however, that nasal bacteria are necessarily the cause of the disease, nor that modifying them would prevent it. But the laboratory's work aims precisely to clarify these mechanisms and to confirm them in humans.

At the end of the same corridor, behind a navy blue door, several researchers are interested in another extremely widespread illness: depression. Most antidepressants, like Prozac, work to extend the life of serotonin in the brain. However, their work has shown that in the event of an imbalance in the intestinal microbiota, the blood composition of amino acids decreases and the synthesis of serotonin is reduced. By restoring the microbiota of “depressed” mice, they regain sensitivity to antidepressants.