Loss of nerve cells is a process that can take place not only in the brain, but also in the (less well-known) nervous system in the gut. A new study, carried out at KU Leuven and published in Nature, shows that specialised immune cells shape this nervous system, enabling the gut to make the transition to solid food early in life. At a later stage, these immune cells take on another role – they start protecting and maintaining the nerve cells.
Specialised immune cells, known as macrophages, play a crucial role in the nervous system in the gut. This is shown by new KU Leuven research lead by gastroenterologist Guy Boeckxstaens. Research in mice shows that the proper functioning of macrophages is crucial for the organisation of nerve cells into a network just after birth, and later for their maintenance in accordance with proper digestion.
“Indeed, we see that macrophages can perform several functions in line with the specific requirements of the nerve cells,” Professor Boeckxstaens explains. “In the first phase of life, they take care of maturing the nervous system: the macrophages eat, as it were, the redundant nerve cells and provide the right structure. This is necessary for the transition from liquid to solid food. Once this maturation is complete, the nerve cells send a signal to the macrophages, using the molecule TGF-ß, with the instruction to no longer to eat the nerve cells, but instead to start nurturing them."
“Until now, it had been unclear what mechanisms caused the nervous system in the gut to 'mature' after birth and enable the gut to process solid food,” says Guy Boeckxstaens. “Some infants need more time to tolerate solid food and be able to process it. This could well be down to delayed action by this specific population of macrophages.”
The research shows the importance of proper interaction between the immune system and the nervous system of the gut. Thus, the perfect interaction between nerve cells and macrophages is fundamental to ensure the health of the guts nervous system and digestion. If the immune cells do not function well, or too well, the quantity of nerve cells and – by consequence – the function of the gut will be affected too, with delayed gastric motor activity and constipation or diarrhoea as a result. These symptoms are characteristic for the loss of nerve cells in the gut in diseases such as diabetes, or in obesity and old age. A disrupted interaction between macrophages and nerve cells may well play a role in this.
The interaction between the nervous system and the immune system in the gut, and how this may give rise to abnormal gut function and certain health problems, remains a relatively new area of research.
“At present, we are still working apace to identify the basic mechanisms for the loss of nerve cells – also known as neurodegeneration – in the gut,” says Guy Boeckxstaens. “Hopefully, we'll be able to track down some new targets for monitoring this process over time that way. And who knows? This gut research might also give us some new insights into what goes wrong with neurodegenerative conditions in the brain, in which similar macrophages also play a major role. We don't call the nervous system of the gut the 'little brain' for no reason.”
The study ‘Dedicated macrophages organize and maintain the enteric nervous system’ by Viola et al. was published in Nature. (doi: 10.1038/s41586-023-06200-7)
The research was funded by the European Research Council (ERC Advanced Grant: ERC-833816-NEUMACS).