Study brings new insights into the development of and care for the ‘little brain’ in the intestine

Loss of nerve cells can take place not only in the brain, but also in the (lesser known) nervous system in the intestine. A new study, conducted at KU Leuven and published in Nature , shows that specialized immune cells shape this nervous system to enable the transition to solid food. In a later phase, the immune cells take on a different role and protect and maintain the nerve cells.

Specialized immune cells, called macrophages, play a critical role in the nervous system of the gut. This has emerged from new KU Leuven research, led by gastroenterologist Guy Boeckxstaens. Research in mice shows that the proper functioning of macrophages is crucial to structure the nerve cells into a network shortly after birth and to maintain it later in function of good digestion.

“We indeed see that macrophages can perform different functions according to the specific needs of the nerve cells,” explains Professor Boeckxstaens. “In the first phase of life, they ensure the maturation of the nervous system: the macrophages, as it were, eat up the excess nerve cells and provide the correct structure. This is necessary to make the transition from liquid to solid food. Once this maturation is complete, the nerve cells send a signal to the macrophages, through the molecule TGF-β, instructing them to stop eating the nerve cells, and start caring for them.”

“Until now, it was unclear which mechanisms ensure that the intestinal nervous system ‘matures’ after birth and enables the intestine to process solid food,” says Guy Boeckxstaens. “Some infants need more time to tolerate and process solid foods. Perhaps that is the result of a delayed action of this specific population of macrophages.”


Who knows, the study of the gut may provide us with new insights into what goes wrong in neurodegenerative disorders in the brain, in which similar macrophages also play an important role.

Unexplored territory
The research shows the importance of a good interaction between the immune system and the nervous system in the gut. A perfect interaction between nerve cells and macrophages is thus fundamental to ensure the health of the intestinal nervous system and digestive system. If either is present in too much or too little, the amount of nerve cells and consequently intestinal function is affected, resulting in delayed gastric emptying and constipation or diarrhoea. These symptoms are characteristic of the loss of nerve cells in the gut in diseases such as diabetes or in obesity and aging. A disturbed interaction between macrophages and nerve cells may play a role in this.

The interaction between the nervous system and the immune system of the gut, and how this can lead to abnormal gut function and certain health problems, is still a relatively young field of research. “At the moment we are still very busy mapping the basic mechanisms of the loss of nerve cells, also known as neurodegeneration, in the intestine,” says Guy Boeckxstaens. “Hopefully we will be able to track down new targets to control this process in the long term. And who knows, the study of the intestine may also provide us with new insights into what goes wrong in neurodegenerative disorders in the brain, in which similar macrophages also play an important role. We don’t call the nervous system of the gut the ‘little brain’ for nothing.”