French scientists have discovered elements of the intestinal microbiota in the brains of rodents. How did they get there and what role do they play? In particular on appetite regulation? The answer gives hope for better management of obesity.
The intestinal microbiota, made up of billions of bacteria, is essential to our good health. It acts at the digestive level but also at the metabolic, immune and neurological level. Over the course of studies, the brain no longer appears as a separate organ but in communication with all the other organs of our body. “It’s been a few years now that we realize that in neuroscience, the answers are no longer located only in the cranial box.“says Pierre-Marie Lledo, CNRS researcher and head of the Perception and Memory Unit at the Pasteur Institute. The one who had already highlighted the link between chronic stress, microbiota imbalance and depression then became interested in to inflammatory diseases like Crohn’s disease, which are known to be associated with mood disorders.”In humans, the mutation of the Nod2 receptor is known to be a susceptibility factor for these specific chronic inflammatory diseases” Pierre-Marie Llédo. “It is well known to be expressed by the immune system to allow the body to react to invader, intruder, bacteria“. However, with his team, he discovered that it was also expressed in the brain.
From the gut to the brain, bacteria travel
Disseminated in several areas, Nod2 was spotted 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 rise to the brain?
What justifies its presence, what information does it exchange with the brain? This is the question posed by these researchers from INSERM, 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 the expression of the receptor in the neurons of the hypothalamus influences satiety. So when we eat, we ingest bacteria that proliferate in the intestine 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 fullsums up Pierre-Marie Lledo.
The process of satiety impeded
The microbiota therefore communicates directly with the brain, allowing it to control food intake. Could disorders such as bulimia, diseases such as obesity or diabetes be apprehended differently in the light of this discovery? Certainly believes the researcher. “This is where we realize that the expression of free will – have I eaten enough, will I have more cheese – does not depend so much on our decision but rather on these fragments of bacteria which manage to reach our brain and inhibit the appetite center found in the hypothalamus. They act as a local anesthetic on the phenomenon of satiety“.
As part of the investigation, 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. It is also possible that we discover that the microbiota sends the wrong signals because of an unbalanced diet, too low in fiber or too sweet for example. Perhaps also that taking antibiotics disrupts the intestinal flora to the point of upsetting the proper functioning of the hypothalamus. So many avenues that remain to be explored.