Stress alters the gut microbiota and increases infection risk, mouse study suggests

The findings suggest that the vagus nerve and amygdala are crucial in maintaining microbiota balance and could serve as targets for mitigating stress-related gut and immune conditions.
Table of Contents

What is already known
Psychological stress can alter microbiota composition, reducing beneficial bacteria such as Lactobacillus and increasing susceptibility to infections. Studies in humans and animals have shown that stress affects mucosal immunity, but how brain states control mucosal secretion in ways that affect the microbiota remains unclear.

What this research adds
Working in mice, researchers removed glands responsible for producing mucus in the gut and found that the animals were unable to combat bacterial infections and showed excessive inflammation. Gland removal also eliminated Lactobacillus bacteria, which help produce proteins involved in the integrity of the gut lining. Without these bacteria, the gut walls became permeable, allowing harmful substances to enter the bloodstream and trigger an immune response and inflammation. Further analyses revealed that nerve cells in the glands are directly connected to the vagus nerve, which extends to the amygdala — a brain region involved in stress processing.

Conclusions
The findings suggest that the vagus nerve and amygdala are crucial in maintaining microbiota balance and could serve as targets for mitigating stress-related gut and immune conditions.

Psychological stress can alter microbiota composition, reducing beneficial bacteria and increasing susceptibility to infections. Now, research in mice shows that stress can cause the brain to send signals to gut glands that lead to elimination of a type of bacteria that prevent inflammation.

The findings, published in Cell, suggest that the nervous system is crucial in maintaining microbiota balance. The results also point to targets for mitigating stress-related gut and immune conditions.

Previous studies have shown that when an organism is stressed, the brain signals organs to release hormones that can sometimes trigger inflammatory bowel disease. Stress can also affect mucosal immunity, but how brain states control mucosal secretion in ways that affect the microbiota remains unclear.

To address this question, researchers led by Hao Chang at Icahn School of Medicine at Mount Sinai in New York examined the communication pathways between the mouse brain and gut. 

Gut glands

The team focused on a type of gut glands called Brunner’s glands, which are located in the walls of the small intestine and are responsible for producing mucus that helps digested food move through the gut. Because previous work suggested that Brunner’s glands contain nerve cells, the researchers hypothesized that the vagus nerve, which connects the brain to the Brunner’s glands in the gut, could help explain how brain states influence the microbiota.

Removing Brunner’s glands impaired the mice’s ability to combat bacterial infections and resulted in inflammation and excessive immune activation. This effect was similar to what people experience after gland removal due to tumors, the researchers say. 

Gland removal also eliminated Lactobacillus bacteria, which help produce proteins involved in the integrity of the gut lining. Without these bacteria, the gut walls became permeable, allowing harmful substances to enter the bloodstream and trigger an immune response and inflammation.

Brain connection

Further analyses revealed that nerve cells in Brunner’s glands are directly connected to the vagus nerve, which extends to the amygdala — a brain region involved in stress processing. Administering probiotics to mice lacking Brunner’s glands mitigated the negative effects associated with gland removal. 

“While Lactobacillus and Bifidobacteria administration restored the integrity of the gut barrier and lessened sympathetic nerve activity, antibiotic-treated animals displayed enhanced gut permeability,” the researchers say.

Inducing stress in mice with intact Brunner’s glands produced symptoms similar to those seen after gland removal, the team found. The results indicate that the vagus nerve and the amygdala play essential roles in maintaining microbiota balance and could be targeted to help alleviate stress-related gut and immune conditions.