Scientists have found immune cells in mice and human intestines impacting the gut microbiome, which in turn could affect brain functions linked to stress-induced disorders such as depression.
The changes brought about by these immune cells could potentially provide new targets for drugs or therapies to treat depression, the team of scientists, led by Johns Hopkins Medicine (US) researchers, said in a study.
Scientists have found immune cells in mice and human intestines impacting the gut microbiome, which in turn could affect brain functions linked to stress-induced disorders such as depression.
The changes brought about by these immune cells could potentially provide new targets for drugs or therapies to treat depression, the team of scientists, led by Johns Hopkins Medicine (US) researchers, said in a study.
"The results of our study highlight the previously unrecognized role of intestinal gamma delta T cells in modifying psychological stress responses, and the importance of a protein receptor known as dectin-1, found on the surface of immune cells, as a potential therapeutic target for the treatment of stress-induced behaviors," says Atsushi Kamiya, study's senior author and professor at the Johns Hopkins University School of Medicine, US.
The results have been published in the journal Nature Immunology. Immune cells get the signal to activate themselves in specific ways when dectin-1 binds to certain antigens, or proteins.
This receptor, the researchers said, could be involved in the microbiome alteration and immune-inflammatory responses in the colon of mice, suggesting that it could be involved in stress responses via gamma delta T cells in the intestinal immune system.
Kamiya and team designed experiments aimed at understanding stress-induced behaviours brought about by an imbalance in the gut microbiota - types of microorganisms found in a specific environment, such as bacteria, fungi and viruses. The experiments were based on previous studies which suggested a link between immune inflammatory responses in the gut and depression.
The team studied the effects of chronic social defeat stress (CSDS), a standard rodent test to study stress-induced disorders such as depression, on the mice's gut microbiota, the study said.
The study classified the mice into two groups - stress-resilient (stress did not diminish social interactions) and stress-susceptible (stress increased social avoidance).
The mice were assessed based on their responses to potentially stress inducing environments that could mimic similar responses in human environments, simulated by researchers. Fecal samples were then collected and genetically analysed to determine the diversity of bacteria in the mice's gut microbiota, the study said.
The analysis showed that the intestinal organisms were less diverse in stress-susceptible mice than in stress-resilient mice. It specifically revealed that there were less Lactobacillus johnsonii (L. johnsonii) - a type of probiotic, or "good" bacteria - in stress-susceptible mice compared to stress-resilient mice.
"We found that stress increased the gamma delta T cells, which in turn increased social avoidance," said Xiaolei Zhu, study's lead author and assistant professor at the School.
"However, when the stressed mice were given L. johnsonii, social avoidance decreased and the gamma delta T cells went to normal levels, suggesting that CSDS-induced social avoidance behavior may be the result of lower levels of the bacteria and gamma delta T cell changes," said Zhu.
The scientists also conducted assessments to understand how the gut microbiota alterations could impact the human brain. They investigated the makeup of gut organisms in people with major depressive disorder (MDD) compared to people without MDD.
In these assessments, the researchers found that the relative abundance of Lactobacillus was inversely related to higher depression and anxiety scores in the MDD group, meaning that the more Lactobacillus found in the gut, the lower the potential for depression and anxiety.
"Despite the differences of intestinal microbiota between mice and humans, the results of our study indicate that the amount of Lactobacillus in the gut may potentially influence stress responses and the onset of depression and anxiety," said Kamiya.
"These early-stage findings show that, in addition to probiotic supplements, targeting drugs to such types of receptors in the gut immune system may potentially yield novel approaches to prevent and treat stress-induced psychiatric symptoms such as depression," said Kamiya.