Stress may do much more than affect your mood—it could also weaken your immune system and speed up the aging of blood-forming stem cells. A new study has uncovered a previously unknown connection between the brain, gut and bone marrow, offering fresh insights into how prolonged psychological stress may increase the risk of illness and age-related diseases.

The study, published in the journal Cell Stem Cell, suggests that chronic psychological stress can disrupt the gut microbiome, reducing the production of a beneficial compound called spermidine. This, in turn, may impair the function of hematopoietic stem cells (HSCs)—the cells in bone marrow responsible for producing all blood and immune cells.

Researchers say the findings, although based on a mouse model, reveal a biological pathway through which emotional stress can influence the body's immune system.

The research was led by Dr. Meng Zhao, Professor at the Zhongshan School of Medicine at Sun Yat-sen University in China. According to Dr. Zhao, the study was inspired by a common observation that people often become more vulnerable to infections during periods of prolonged stress.

"Psychological stress is increasingly recognized as an important risk factor for diseases such as cancer, cardiovascular disease and age-related disorders. However, we still know very little about how emotional stress sends biological signals that affect distant organs," he said.

Using a mouse model, the researchers found that chronic stress reduced the ability of bone marrow stem cells to renew themselves and lowered the production of lymphocytes, a key type of white blood cell involved in fighting infections.

Further investigation revealed that stress triggers signals from the brain through the sympathetic nervous system to the intestine. These signals alter the gut environment and change the composition of gut bacteria, reducing levels of spermidine—a naturally occurring molecule known for supporting healthy aging and normal cell function.

Without enough spermidine, the stem cells in the bone marrow gradually lose their ability to produce healthy blood and immune cells, ultimately weakening the body's defence system.

The study also identified two brain regions—the medial prefrontal cortex and the periaqueductal gray—as key regulators of this newly discovered brain-gut-bone marrow pathway. Suppressing activity in these areas produced immune and blood cell abnormalities similar to those caused by chronic stress.

According to the researchers, this is the first direct evidence that specific brain circuits can regulate the function of blood-forming stem cells in the bone marrow.

Dr. Zhao said identifying these brain regions could eventually help scientists develop new therapies to preserve immune function in people living with chronic psychological stress.

The research team now plans to investigate whether the same brain-gut-bone marrow pathway exists in humans and whether it contributes to immune dysfunction associated with aging, cancer and other chronic diseases.

Experts not involved in the study have described the findings as an important advance in understanding how stress affects the entire body.

Dr. Ashkan Farhadi, a gastroenterologist at MemorialCare Orange Coast Medical Center in California, said scientists have long recognised the two-way communication between the brain and the gut, which was later expanded to include the gut microbiome. This study, he said, extends that connection to the bone marrow and overall immune health.

He noted that the research highlights how psychological stress can influence multiple organs by first altering the gut and its microbial community.

Similarly, Dr. Dung Trinh, Chief Medical Officer of the Healthy Brain Clinic in California, called the study "fascinating" because it connects the brain, gut microbiome, immune system and aging through a single biological pathway.

He cautioned, however, that the findings are based on animal studies and do not yet prove that the same mechanism operates in humans. Further clinical research will be needed before the results can be translated into medical practice.

While scientists continue to explore the biological effects of stress, health experts recommend practical measures to reduce its impact. Regular physical activity, deep breathing exercises, adequate sleep, limiting alcohol, caffeine and excessive social media exposure, and maintaining strong social connections can all help manage stress. They also advise seeking professional support if anxiety, depression or chronic stress becomes overwhelming.

The findings add to the growing body of evidence that mental health and physical health are closely connected, suggesting that managing stress may not only improve emotional well-being but also help protect the immune system and support healthier aging.