A growing body of evidence reveals the degree of interdependence between hosts and their gut microbiota and illustrates the importance of the gut-brain axis in human health. Gut microbiota by-products are known to circulate in the bloodstream, regulating host physiological processes, including immunity, metabolism but also brain function. This is a first established link between the microbiota and the brain. The Institut Pasteur team with colleagues from Inserm and CNRS revealed, in an animal model, that hypothalamic neurons directly detect variations in bacterial activity and adapt appetite and body temperature accordingly. These discoveries also illustrate the direct dialogue that takes place between the intestinal microbiota and the brain and suggest new therapeutic approaches against metabolic disorders such as diabetes and obesity.
A receptor involved in both bacterial activity in the gut and neural activity in the brain
Scientists are focusing here on a receptor, NOD2, present inside most immune cells. This receptor detects the presence of muropeptides, building blocks of the bacterial cell membrane. Furthermore, variants of the gene encoding the NOD2 receptor are known to be associated with digestive disorders, including Crohn’s disease, as well as with neurological diseases and mood disorders. Thus, NOD2 appears involved in bacterial activity in the intestine in neuronal activity in the brain.
The study: Using brain imaging techniques, scientists observed in mice that:
- NOD2 in mice is expressed by neurons in different regions of the brain and in particular in the hypothalamus;
- these hypothalamic neurons are involved in the regulation of appetite and body temperature;
- however, their electrical activity is suppressed when they come into contact with bacterial gut muropeptides;
- but if the NOD2 receptor is absent, the activity of these neurons is no longer inhibited by muropeptides and the brain then loses control of food intake and body temperature: the study shows that mice gain weight and are more likely to develop type 2 diabetes.
It is therefore the demonstration of a direct dialogue between neurons and bacteria: neurons directly perceive bacterial muropeptides and that these bacterial fragments act directly on the hypothalamus, an area known to manage vital functions such as body temperature, reproduction, hunger and thirst. Bacterial activity therefore “serves” for the brain as a direct indicator of the impact of food intake on the intestinal ecosystem.
These muropeptides which could exert other influences on the neurons of the hypothalamus and ultimately on other cerebral and metabolic functions, will lead to new therapeutic approaches…brain diseases and metabolic disorders.