The Virome Regulates the Effects of Chronic Stress in Mice

The microbiota-gut-brain axis plays a vital role in how our bodies respond to stress, but most research has focused on the bacteria in our gut. However, the gut also contains a significant number of viruses called bacteriophages or phages. These viruses can influence the structure and function of the gut’s bacterial community. Studies have shown that treatments using phage-rich faecal filtrates can improve the gut’s microbial balance and the health of the host in cases like Clostridioides difficile infection, antibiotic-related gut disruptions, and type 2 diabetes. Here, we wondered whether chronic stress might not only affect the gut’s bacteria but also its viral composition. To find out, we conducted a transplant of the viral content from the faeces of unstressed mice into mice experiencing chronic social defeat stress. We found that chronic stress caused changes in behaviour, immunity, and the gut’s bacterial community, which were also reflected in viral changes. The viral transplant improved stress-coping behaviours and restored stress-induced physiological changes in the mice. It also had positive effects on the immune system, reducing inflammation. Furthermore, the transplant restored certain beneficial bacteria and reduced harmful ones affected by stress. In specific brain areas sensitive to stress, the transplant restored genes that were disrupted, particularly in the amygdala, which is linked to fear and emotional processing. Therefore, we conclude that stress can alter the gut’s virome, and introducing a healthy viral population can help with stress coping. The treatment also has broad positive effects on the immune system and behaviour.