Postdoctoral researcher Han Eui-jeong (from left), researcher Kim Da-hye and principal researcher Jeong Hye-jong, who conducted the study. [KBSI]
Postdoctoral researcher Han Eui-jeong (from left), researcher Kim Da-hye and principal researcher Jeong Hye-jong, who conducted the study. [KBSI]

Scientists have identified beneficial gut microbes with strong potential for alleviating depression under chronic stress conditions.

A research team led by Jeong Hye-jong at the Honam Center of the Korea Basic Science Institute (KBSI) announced Monday that it had identified two key gut microbes associated with depression-like behavior under chronic stress and had uncovered the molecular mechanisms by which these microbes influence oxidative stress and neurotrophic signaling in brain neurons.

Depression is one of the most common mental disorders worldwide, with chronic stress and prolonged exposure to stress hormones among its primary causes. Sustained stress is known to increase oxidative stress within cells and impair mitochondrial function — the organelles responsible for energy production — thereby disrupting the BDNF (Brain-Derived Neurotrophic Factor) signaling pathway, which plays a critical role in neuronal survival and neural plasticity.

While a growing body of research has shown that gut microbiota can influence brain function and behavior, it has remained unclear which specific microbes are involved in stress responses and depression-like behavior, and through what biological mechanisms they regulate brain function.

The team used fecal microbiota transplantation-based analysis to identify gut microbes consistently reduced in mice exhibiting higher levels of depression-like behavior. Two species — Intestinimonas butyriciproducens and Parabacteroides merdae — emerged as key candidate strains associated with depressive behavior.

A schematic diagram showing how gut microbiota directly regulate intracellular signaling pathways in neurons via the gut-brain axis. [KBSI]
A schematic diagram showing how gut microbiota directly regulate intracellular signaling pathways in neurons via the gut-brain axis. [KBSI]

Cell and animal experiments confirmed that both strains reduced the production of reactive oxygen species in neurons and alleviated oxidative stress. They also suppressed mitochondrial dysfunction and apoptotic signaling while restoring the signaling pathways critical for neuronal growth and survival.

In an animal model where depression-like behavior was induced by administering corticosterone, a chronic stress hormone, oral administration of the two strains significantly reduced depression-like behavior.

The findings suggest that the severity of depressive behavior may be shaped not simply by a reduction in overall gut microbial diversity, but by the presence and functional characteristics of specific gut microbes.

"This research has demonstrated that specific gut microbes can directly regulate intracellular signaling pathways in neurons via the gut-brain axis," Jeong said. "We expect it will contribute to the development of next-generation microbiome-based precision medicine for the prevention and treatment of depression."

The study, supported by the National Research Foundation of Korea, was published in the international pharmacology journal Pharmacological Research.


nbgkoo@heraldcorp.com