Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal, and immunological levels
An exciting new concept is emerging in health and disease is the capability of microbiota in the gut to establish communication with the human brain and alter its behaviour. This can introduce a new arena, that when people make decisions, whether they are influenced by the microbiota of their gut or not. The bidirectional communication between the brain and the gastrointestinal tract is essential for keeping homeostasis. This signalling is regulated at hormonal, neural (both enteric and central nervous systems) and immunological levels. Disturbing these systems leads to modifications in stress levels and general behaviour. There is an elevated co-morbidity noted between anxiety and other psychiatrically-related symptoms and various gastrointestinal disorders, like irritable bowel disorder (IBS). This is why it is essential to learn the exact mechanism of this communication.
One of the approaches used to research the connection between microbiota of gut and brain is by using experimental animal models. Germ free mice which completely lack contamination from any sort of gut bacteria offer great possibilities for research. Female germ-free mice were used to show the lack of conventional microbiota leads to anxiety level being reduced in one study while the other showed that there was increased responsiveness to stress with male mice that were free of germs. The reasons for the results being different are not familiar at the moment, but it is presumed that gender might play a role when it comes to these effects. One more important aspect to consider regarding the recent data is that male animals suffered some endocrine and neurochemical effects of growing up in an environment free of germs, but there were no noted immune effects. Of course, this doesn’t mean that this could exactly be the real situation with humans, but the researchers did generate some insightful data on whether microbiota can change one’s behaviour or not.
Probiotics are important and can help in the treatment of various gastrointestinal disorders such as Irritable bowel syndrome (IBS). There are clinical studies that show that using probiotics causes the IBS patients to be in a better mood and reduces their anxiety. The mechanism of action remains unclear, but it is determined that certain probiotics have the possibility to lower inflammatory cytokines; enhance the nutritional status and lower oxidative stress. It is clear that there are probiotic agents that can alter certain aspects of the microbiota-gut-brain axis and, therefore, influence the brain and behaviour.
Intervention with antibiotics has been known to cause the reduction of biodiversity of the fecal microbiota, postponing the colonization by some probiotic agents. Use of antibiotics was the most convenient artificial way to create dysbiosis of the intestines with animals used in experiments. After allowing antibiotics to disturb the microbiota for a period of 7 days, mice have shown either anxiety reduction as well as an enhancement in locomotor behaviour. There are also studies that showed that rats induced with stress during early life expose signs of modified behaviour and modifications of fecal microbiota in their adult life.
There are studies that observed animal behavior after having an infection but failed to show a clear way the gut is communicating with the brain, offering a solution that there are multiple routes. Mice that were infected with Citrobacter rodentium showed some increase in behavior similar to anxiety after 7 or 8 hours from getting infected, but there was no influence on their behavior after two weeks or a whole month. The infection and the psychological stress can jointly affect the CNS, but since no overt inflammation was noticed and an increase in neuronal activation didn’t happen in vagal ganglia, it is thought that the signaling between the gut and the brain is done through the vagus nerve.
Another study that showed the involvement of the vagus nerve to communicate from the gastrointestinal tract to CNS was when a Salmonella Typhimurium was used for an infection. The results once again showed that vagus plays a role of huge matter in signaling immune information from gut to brain, as well as in homeostasis related with the immune system. However, there were other studies, such as the one where Campylobacter jejuni was used in mice, which showed some implications of the vagal nerve in the effect of communicating this pathogen and its effects to the brain.
Many studies were conducted in the recent years and that shows that the need for understanding cellular, molecular and physiological foundation of communication between enteric microbiome gut and brain is essential. This is something that remains to be discovered and future studies. This issue will also be a topic at the Awaremed’s Network Integrative Addiction Conference, which can be a great opportunity to meet fellow professionals and share your opinions and experiences. If you want to sign up for the conference, you can do it here.