How intestinal bacteria can cause depression

It has been known for quite some time that the proverbial “gut feeling” has a real medical basis. The intestine has its own nervous system, also known as the “abdominal brain” owing to its size and complexity, and it is closely connected to the brain. Processes in the intestine cause changes in the brain and, conversely, psychological factors influence the intestine. How far this interaction goes and how exactly it works, however, has not yet been fully understood. There are indications that the intestine may be involved in the development of psychiatric diseases. A research group headed by the neuropharmacologist and neurogastroenterologist Peter Holzer from Graz was able to identify a number of concrete factors that can trigger psychological changes in mice in a recently completed basic-research project funded by the Austrian Science Fund FWF.

Intestine affects the brain

“The connection between the intestinal nervous system and the brain has been known for a long time, but the situation has become more complex if you consider the most recently published studies,” says principal investigator Peter Holzer. “In addition to the direct neural pathways between intestine and brain, which we have known about for a long time, there are many intestinal hormones that carry messages to the brain, as well as a huge immune system that releases messenger substances when stimulated. In recent years, the gut microbiota has become an additional factor. This consists of a huge number of monocellular organisms that also release substances and are believed to play an important role in the body’s information system.” According to Holzer, many people are familiar with a strong connection between brain and gut. “But we are not usually aware of such an amount of information reaching the brain from the gut. This information is fed into brain areas that are important for our mood and emotions.”

Feeling ill because of bacteria in the intestine

Holzer and his team have spent five years investigating various signalling pathways which intestinal processes can use to influence the brain. One objective of the project was to clarify how certain bacteria in the gut alert the immune system and thus trigger a feeling of illness. “The immune system learns early on to tolerate the microorganisms in the gut. That starts in infancy,” explains Holzer. “When some substances produced by bacteria penetrate the intestinal wall, this certainly creates an immune reaction and, associated with it, a sense of being ill.” Specifically, he investigated the so-called “endotoxin lipopolysaccharide” (LPS), which is released by certain intestinal bacteria and stimulates the immune system, giving us a sense of being ill. “If you suffer an infection with bacteria you will feel tired, have muscle pain, lose your appetite and become withdrawn. This is a sensible reaction of the body, helping it to cope quickly with the infection,” says the researcher. “There is evidence, however, that this reaction could be triggered in humans by intestinal bacteria, even when there is no infection at all.” Holzer’s team were able to show that other substances produced by bacteria, so-called “peptidoglycans”, enhance the effect of LPS. “We believe that lipopolysaccharide is only one of several factors contributing to the development of mental illness.”