Gut Microbes Reduce Stress-Induced Depression-like Behaviors... Mechanism of Brain Signal Restoration Identified [Reading Science]

KBSI Identifies Two Key Gut Microbes Linked to Depression-like Behaviors
Suggests Potential for Microbiome-based Precision Therapies

A team of Korean researchers has discovered two gut microbial species that alleviate depression-like behaviors caused by chronic stress and restore impaired brain neurotrophic signaling. By identifying the molecular mechanism through which specific gut microbes regulate neural cell function via the "gut-brain axis," the study suggests new possibilities for developing microbiome-based technologies for the prevention and treatment of depression.

The Korea Basic Science Institute (KBSI) announced on July 14 that a research team led by principal researcher Hyejong Jeong at the Honam Center had identified two core gut microbial species associated with depression-like behaviors in a chronic stress environment. The team also elucidated the mechanism by which these microbes regulate oxidative stress in brain nerve cells and the neurotrophic signaling pathway. The research findings were published online in the international pharmacology journal Pharmacological Research on May 28.

Schematic diagram showing the process by which two types of gut microbes reduce oxidative stress and restore brain-derived neurotrophic factor (BDNF) signaling to alleviate depression-like behavior in mice induced by chronic stress. Provided by the research team

First Identification of Two Gut Microbes Linked to Depression-like Behaviors

Depression is a leading mental disorder caused by chronic stress and continuous exposure to stress hormones. While recent studies have shown that gut microbes can influence brain function and behavior, exactly which microbes are involved in depression-like behaviors and how they work have remained unclear.

The research team analyzed gut microbes that were commonly reduced in mice exhibiting severe depression-like behaviors after transplanting human fecal microbiota. As a result, they identified two key candidate strains: Intestinimonas butyriciproducens and Parabacteroides merdae.

Through subsequent cell and animal experiments, the team confirmed that these two strains reduce the production of reactive oxygen species in nerve cells, thereby alleviating oxidative stress and restoring impaired mitochondrial function.

Restoration of Brain Neurotrophic Signaling... Reduced Depression-like Behaviors in Animal Experiments

The researchers also found that these strains help recover the TrkB-ERK-CREB-BDNF signaling pathway, which is essential for the growth and survival of nerve cells.

Research team photo. (From left) Han Eui-jung, postdoctoral researcher at the KBSI Honam Center (first author), Kim Dahye, researcher (co-author), Jung Hyejong, senior researcher (corresponding author).

In particular, when the strains were administered orally to mice that had been induced to display depression-like behaviors through the administration of the stress hormone corticosterone, depression-like behaviors significantly decreased, and expression of BDNF in the hippocampus—a region responsible for memory and emotion—was restored.

The research team explained that this study demonstrates depression-like behaviors can be influenced not just by a reduction in microbial diversity, but by the presence and function of specific gut microbes. They also emphasized the significance of presenting a biological mechanism in which gut microbes jointly regulate oxidative stress, mitochondrial function, and neurotrophic signaling to affect stress responses and depression-like behaviors.

Hyejong Jeong, principal researcher at KBSI, stated, "We have identified that specific gut microbes can directly regulate neural signaling pathways via the gut-brain axis," adding, "We expect these findings will contribute to the future development of microbiome-based precision medicine technologies for the prevention and treatment of depression."

This content was produced with the assistance of AI translation services.