Unravelling the immune-gut-brain axis in severe mental illness: From mechanisms to treatment

Depression, bipolar disorder, and schizophrenia-spectrum disorders are serious mental illnesses that disturb mood, thinking and daily life, shorten life expectancy, and create heavy personal and social costs. While treatments exist, many people don’t fully recover, and some symptoms, like memory problems or low motivation, often persist.
This thesis explores how the immune system and gut may be involved in these conditions. The immune system doesn’t just fight infections; it also communicates with the brain. We found that people with psychiatric disorders show signs of immune imbalance, especially those with treatment resistance, early-life trauma, or metabolic problems. These immune changes may be linked to difficulties in thinking and motivation. In people with bipolar disorder, we observed unusual patterns in immune cells and stronger responses to common viruses. In newly diagnosed schizophrenia patients, we found early signs of oxidative stress, suggesting disturbances may appear early in the illness.
The gut also plays an important role. We found that people with mental illness have a different mix of gut bacteria compared to healthy individuals. Certain types were more common in patients, while beneficial ones were reduced. We also found that a probiotic supplement was safe, helped strengthen the gut lining and boosted memory. Interestingly, the gut bacteria someone starts with may influence how well they respond to such treatments.
Our findings suggest that mental illness also involves the body. Supporting immune and gut health through targeted probiotics, anti-inflammatory strategies, healthy diets, and physical activity alongside traditional treatments may be an important part of treating mental illness.