A new study by the Farncombe Family Digestive Health Research Institute, published in the journal of Nature Communications, has revealed that intestinal bacteria may induce depression and anxiety. The gut bacteria communicate with their host in a bidirectional manner based upon life stress and affect neurotransmitters in the brain.
“We have shown for the first time in an established mouse model of anxiety and depression that bacteria play a crucial role in inducing this abnormal behaviour,” said Premysl Bercik, senior author of the paper and an associate professor of medicine with McMaster’s Michael G. DeGroote School of Medicine. “But it’s not only bacteria, it’s the altered bi-directional communication between the stressed host — mice subjected to early life stress — and its microbiota, that leads to anxiety and depression.”
Researchers used a mouse model to induce life stress through maternal separation. Conventional mice with complex microbiota, which had been maternally separated, displayed anxiety and depression-like behaviour, with abnormal levels of the stress hormone corticosterone. These mice also showed gut dysfunction based on the release of a major neurotransmitter, acetylcholine.
Mice who did not have the bacteria, but were maternally separated, still showed altered stress hormone levels and gut dysfunction but they did not show symptoms of anxiety or depression.
When the bacteria free mice were colonized with bacteria from the mice exhibiting anxiety and depression, the bacterial composition and metabolic activity of the germ free mice changed within a few weeks and mice started exhibiting anxiety and depression.
“However, if we transfer the bacteria from stressed mice into non stressed germ-free mice, no abnormalities are observed. This suggests that in this model, both host and microbial factors are required for the development of anxiety and depression-like behavior. Neonatal stress leads to increased stress reactivity and gut dysfunction that changes the gut microbiota which, in turn, alters brain function,” said Bercik.
“We are starting to explain the complex mechanisms of interaction and dynamics between the gut microbiota and its host. Our data show that relatively minor changes in microbiota profiles or its metabolic activity induced by neonatal stress can have profound effects on host behaviour in adulthood, said Bercik.”
A previous study revealed that serotonin is also produced in the gut. Peripheral serotonin is made in the digestive tract and it is estimated that approximately 90% of all serotonin is produced in the gut. The University of Chicago has published a new study in the journal Cell specifying the metabolic pathway involved. Enterochromaffin (EC) cells and specific type of immune cells and neurons produce peripheral serotonin. The purpose of this study was to investigate the hypothesis that specific types of bacteria are involved in interacting with EC cells to produce serotonin.
“More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,” said Elaine Hsiao, research assistant professor of biology and biological engineering and senior author of the study. “We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.”
“EC cells are rich sources of serotonin in the gut. What we saw in this experiment is that they appear to depend on microbes to make serotonin—or at least a large portion of it,” said Jessica Yano, first author on the paper and a research technician working with Hsiao.
“While the connections between the microbiome and the immune and metabolic systems are well appreciated, research into the role gut microbes play in shaping the nervous system is an exciting frontier in the biological sciences,” said Sarkis K. Mazmanian, Luis B. and Nelly Soux Professor of Microbiology and a coauthor on the study. “This work elegantly extends previous seminal research from Caltech in this emerging field”.
The researchers tested several different single species and groups of known gut microbes. It was determined that the presence of 20 species of spore-forming bacteria—elevated serotonin levels. The mice treated with this specific mix of bacteria also reveal an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.
Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis, Jessica M. Yano et al., Cell, published online 13 April 2015, doi:10.1016/j.cell.2015.02.047, abstract.
G. De Palma, P. Blennerhassett, J. Lu, Y. Deng, A. J. Park, W. Green, E. Denou, M. A. Silva, A. Santacruz, Y. Sanz, M. G. Surette, E. F. Verdu, S. M. Collins, P. Bercik. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nature Communications, 2015; 6: 7735 DOI: 10.1038/ncomms8735