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A groundbreaking study has uncovered a critical brain-gut connection that links psychological states to changes in the gut microbiome, with profound implications for immune function and stress-related health conditions. The research, now published in the journal Cell, reveals how stress-sensitive brain circuits influence the composition of gut bacteria through Brunner’s glands in the small intestine. It sheds light on the intricate mechanisms by which mental states can impact physical health, pointing to new possibilities for therapeutic intervention, for example against inflammatory bowel disease.
The brain and the gut are in constant communication, and this two-way communication between them is crucial for many aspects of health. It is well-established, for instance, that psychological stress reduces the counts of beneficial bacteria in the gut and thereby impairs immunity. However, the precise mechanisms have so far remained unclear.
A new study, conducted by researchers at the Icahn School of Medicine at Mount Sinai (New York) and the Max Planck Institute for Biological Cybernetics (Tübingen, Germany), has now identified a circuit that connects the brain with certain gut glands. These organs, called Brunner’s glands, are located in the upper part of the small intestine and secrete the protein mucin, a main component of the mucus that lines the intestinal wall and serves as a substrate for the growth of beneficial gut bacteria. As the team found out, removing Brunner’s glands from mice resulted in lower counts of Lactobacilli, a genus of bacteria abundant in the small intestine of many animals, including humans. The consequence: with fewer Lactobacilli, the mice were more likely to die from gut infections and showed various signs of systemic inflammation.
A direct link from the amygdala to the gut
The researchers also showed that the brain controls the activity of Brunner’s glands using the vagus nerve as a communication pathway. This nerve, a major part of the parasympathetic nervous system, controls many organ systems throughout the body and has a key role in rest and relaxation. The team established that it connects Brunner’s glands to the amygdala, a brain area responsible for emotional responses. Specifically, fear or anxiety causes the amygdala to decrease its activity and send fewer signals to the vagus nerve. When this happens, Brunner’s glands release less mucus, thereby affecting immunity. In fact, exposing the mice to chronic stress had the same effect on their microbiome composition and health as surgically removing the glands.
“Brunner's glands are more important than previously thought,” commented lead author Hao Chang of the Icahn School of Medicine. “As a unique system controlled by the vagus nerve, they directly link the brain to the gut microbiome.”
Potential therapies for inflammatory bowel disease
The results may explain why psychosocial stress increases the likelihood of infection. At the same time, it offers new ways to counteract this phenomenon: stimulating either the amygdala or the vagus nerve in the stressed mice was sufficient to normalize the mucus secretion and completely reverse the effects of stress on their gut microbiome and immunity. Giving the mice probiotics also appeared to be sufficient to mitigate the negative effects of stress.
The study has broad implications for understanding the relationship between psychological states, gut health, and immunity. By providing a concrete mechanism by which the brain controls the gut microbiome, it offers an explanation for the well-documented link between mental health disorders, such as anxiety and depression, and gastrointestinal and immune conditions. The researchers are now very interested in the clinical applications of their findings: “We believe the glands may be important mediators in inflammatory bowel disease,” said senior author Ivan de Araujo of the Max Planck Institute for Biological Cybernetics. “Studying them further may provide new insights into the disease mechanisms and potential therapies.”
Dr. Hao Chang
Assistant Professor
Nash Family Department of Neuroscience
Icahn School of Medicine at Mt. Sinai
hao.chang@mssm.edu
Dr. Ivan de Araujo
Director
Department Body-Brain Cybernetics
Max Planck Institute for Biological Cybernetics
ivan.dearaujo@tuebingen.mpg.de
Chang, H., Perkins, M., Novaes, L., Qian, F., Zhang, T., Neckel, P., Scherer S., Ley, R.E., Han W., de Araujo, I.E.: Stress-sensitive neural circuits change the gut microbiome via duodenal glands. Cell 187, 1–20, September 19, 2024. Online ahead of print: https://doi.org/10.1016/j.cell.2024.07.019.
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