Chronic psychological stress can influence the immune system, the gut, and inflammation. New research now shows that stress can impair blood-forming stem cells through a brain-gut-bone marrow pathway, making them produce fewer mature immune cells.

The findings, published in Science Advances, suggest that supporting the gut microbiota and its metabolites may help protect the immune system from the biological effects of chronic psychological stress.

Previous work showed that stress can also affect blood production, but how brain stress signals to blood-cell precursors in the bone marrow is unclear. So, researchers led by Xiaobin Tian at Sun Yat-sen University in Guangzhou, China, measured behavior, brain activity, gut microbes, metabolites, and blood-forming stem cell function in several mouse models of psychological stress. 

Stress damage

Across different mouse models, stress made blood-cell precursors act partly “old”: more of these stem cells died in the bone marrow, the remaining cells renewed themselves poorly, and they produced fewer mature immune cells. The damage was especially apparent in precursors that make immune cells such as T cells and B cells. 

The researchers traced these effects to reduced activity in two specific regions of the brain. Turning down either region caused similar stem-cell problems, while turning them back up helped restore stem-cell function.

Stress also lowered levels of spermidine, a molecule that helps cells maintain themselves by supporting cleanup and recycling processes. Giving spermidine back helped the stem cells survive, behave more youthfully, and produce more immune cells.

Gut disruptions

Further experiments showed that stress disrupts gut conditions, reducing helpful Lactobacillus reuteri bacteria, in particular a spermidine-producing L. reuteri strain.

Restoring L. reuteri brought spermidine levels back up and improved stem-cell survival and function, the researchers found. However, spermidine only partly rescued the stem-cell defects, so other stress-related mechanisms are likely involved, the authors say.

“These findings identify a brain-gut-bone marrow axis linking psychological stress to aging-like [hematopoietic stem cells] dysfunction through sympathetic regulation of intestinal microbiota and spermidine metabolism,” they say.