The dialogue between the intestinal flora and the brain could explain certain diseases such as obesity

French scientists have discovered elements of the intestinal microbiota in the brain of rodents. How did they get there and what role do they play? In particular about appetite regulation? The answer gives hope for better management of obesity.

A model of the intestine, in an exhibition on the microbiota at the Cité des Sciences
A model of the intestine, in an exhibition on the microbiota at the Cité des Sciences © AFP / .

The gut microbiota, made up of billions of bacteria, is critical to our good health. It acts at the digestive level but also at the metabolic, immunological and neurological level. Throughout the studies, the brain no longer appears as a separate organ but in communication with all the other organs of our body. “A few years ago we realized that in neuroscience, the answers are no longer found only in the braincase.“says Pierre-Marie Lledo, a CNRS researcher and head of the Perception and Memory Unit at the Pasteur Institute. He who had already highlighted the link between chronic stress, microbiota imbalance and depression, then became interested in diseases inflammatory diseases such as Crohn’s disease, which are known to be associated with mood disorders.In humans, mutation of the Nod2 receptor is known to be a susceptibility factor for these specific chronic inflammatory diseases.” Pierre-Marie Lledo. “It is well known that the immune system expresses it to allow the body to react to invaders, intruders, bacteria.However, with his team he discovered that it was also expressed in the brain.

From the gut to the brain, bacteria travel

Diffused in several areas, Nod2 was detected in the hypothalamus of the rodents studied, a region that controls essential functions such as hunger, temperature, stress, social interactions…

Why do fragments of bacteria go up to the brain?

What justifies its presence, what information does it exchange with the brain? This is the question asked by these researchers from INSERM, the CNRS and the Institut Pasteur. To find out, genetically modified mice lacking Nod2 were bred in the lab for more than a year. If the males did not show any particularity in their development, the females, beyond 6 months, began to grow abnormally. It turns out that receptor expression on neurons in the hypothalamus influences satiety. So when we eat, we ingest bacteria that proliferate in the gut before migrating to the brain (at least the muropeptides) where they inhibit satiety neurons when they interact with the Nod2 receptor. In the end, a bit like having a short circuit, the neurons stop sending the signal. ‘I ate too much, I’m fullsummarizes Pierre-Marie Lledó.

The satiety process impeded

Therefore, the microbiota communicates directly with the brain, allowing it to control food intake. Could disorders such as bulimia, diseases such as obesity or diabetes be apprehended in another way in light of this discovery? The researcher certainly believes. “This is where we realize that the expression of free will – I have eaten enough, I will have more cheese – does not depend so much on our decision but on these fragments of bacteria that manage to reach our brain and inhibit the appetite center that is located in the hypothalamus. They act as a local anesthetic on the phenomenon of satiety“.

As part of the research, Pierre-Marie Lledo and his colleagues will analyze the brains of deceased people to see if the expression of the receptor varies from one individual to another. We may also find that the microbiota is sending the wrong signals due to an unbalanced diet, too low in fiber or too sweet, for example. Perhaps also that taking antibiotics alters the intestinal flora to the point of altering the proper functioning of the hypothalamus. So many avenues left to explore.

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