It’s Not All in Your Head
By: Claire Chang
Our emotions affect almost every aspect of our lives. From the excitement that triggers a flood of adrenaline to the nervousness that clouds our heads during exams, emotion is everywhere — even in our guts.
Stress, as defined by the World Health Organization, is a state of worry or tension brought on by a difficult circumstance. While often linked to symptoms such as headaches or fatigue, stress can also cause conditions such as internal bowel syndrome (IBS) or inflammatory bowel disease (IBD), which influence the gut. But how can stress — an emotional state associated with the mind — affect our guts?
A recent study conducted by Xiao Zheng and other scientists from China explores this connection. “The study focuses specifically on how these signals [of stress] are transmitted to the brain and the gut,” Zheng said. This transmission is facilitated by a specific signaling pathway. In this context, a signaling pathway is defined as a series of chemical reactions that, when accumulated, allow the brain to send signals to various parts of the body — including to the intestinal epithelium, which are the cells that line the inner workings of the stomach.
To explore this dynamic, Zheng observed mice under constant stress and tracked any imbalances in their guts resulting from restraint stress — stress induced by restricting the movement of the mice. To visualize these conditions, the researchers isolated cells from the guts of the mice. “This isolates the complex question with a simplified model,” Zheng explained. The researchers observed that the mice not only lost weight when they were stressed, but they also accumulated a distinct substance within their gut cells. They discovered that signals of stress tell the body to produce more of a certain bacteria called Lactobacillus murinus.
Bacteria, including L. murinus, can serve many functions within the microbiome, including creating metabolites, or proteins that break food down into energy. Indole-3-acetate (IAA), a metabolite created by L. murinus, was shown to disturb the cell differentiation of the intestinal lining, meaning that ordinary stem cells did not develop the proper structures to become an intestinal-lining-specific cell. Though the body is made up of billions of bacteria that coexist in harmony, signals like IAA lead to an imbalance — a disturbance in the stability of the microbiome via the creation of a harmful metabolite. “The major finding is that the metabolite from the bacteria can become the signal that links the brain to the dysfunction of the intestinal stem cells,” Zheng said.
By identifying the specific pathway that allows for this crosstalk between the gut and brain, this study opens the door to possible treatments that can target this pathway to stop L. murinus’s creation, and thereby inhibit any deterrents to intestinal lining cell function. One possible solution includes the oral α-ketoglutarate supplementation, a type of metabolite that, when given to the mice in this study, promoted intestinal cell function by targeting specific signaling pathways.
“In the future, research should investigate the blocking of the specific receptor [within the signaling pathway] to stop the harmful effects of this bacterial metabolite in gut injuries,” Zheng said. By identifying the receptor correlated with IAA, researchers can begin exploring targeted medicines that stop IAA’s harmful downstream effects. In the future, more research is needed to understand the genetic makeup of L. murinus, revealing what sections of the gene should be turned off to stop IAA production.
The body is an amalgamation of signaling pathways brought together by reactions that create metabolites, including stress-related molecules. And these metabolites are brought together through their interactions with the microbiome around them. Stress thus becomes a stimulus that’s not just in your head: it affects your body all over, from the brain to the gut.
