Psychological stress is increasingly recognized as a risk factor for certain health conditions, including cardiovascular disease and diabetes, especially when paired with an impaired immune response. In a study published on July 2 in the journal Cell Stem Cell, researchers describe a mechanism in mice that explains this association: psychological stress speeds up aging-like changes in the body's blood-forming stem cells by altering the intestinal microbiota.
"Our research shows how stress-responsive brain regions regulate the balance of the intestinal microbiota, which ultimately affects the function of hematopoietic stem cells," said senior author Meng Zhao of Sun Yat-sen University in Guangzhou, China.
Previous studies have shown that chronic stress influences immune function and the formation of immune cells in the bone marrow largely through inflammatory pathways and adrenergic receptors. However, how these stress signals were transmitted from the brain to the bone marrow was unclear. In this new study, researchers used four different mouse models of stress to study interactions among the brain, intestine, and bone marrow. They confirmed that chronic stress reduced activity in two brain regions—the medial prefrontal cortex and periaqueductal gray—which induced physiological changes such as loss of hematopoietic stem cells and reduced lymphocyte production.
The team also observed changes in signals sent to the intestines. Specifically, stressed mice had a loss of Lactobacillus reuteri—a species important for maintaining healthy gut microbes—and lowered levels of spermidine, a naturally occurring compound involved in clearing out damaged cells.
"One surprising finding of our study was that suppression of only two specific brain regions was sufficient to produce many of the hematopoietic defects caused by psychological stress," said co-corresponding author Linjia Jiang, also of Sun Yat-sen University. "Alterations in the gut microbiota and in the microbial metabolite spermidine played a crucial role in mediating communication between the brain and bone marrow," Jiang said.
Several questions remain about how psychological stress alters neural circuits across different diseases or whether similar mechanisms operate in humans. The researchers plan further studies on these topics as well as potential interventions to improve bone marrow function during aging or periods of chronic stress. "Although substantial work is needed before clinical translation, these findings provide a conceptual framework for developing new approaches to mitigate immune aging and stress-associated immune dysfunction," Zhao said. "More broadly, our findings raise the possibility that managing psychological stress may not only improve mental well-being but also help preserve immune function and promote healthy aging," Jiang added.
