Stress-induced Changes in Gut Bacteria May Increase Risk of Autoimmune Disorders, Mouse Study Suggests

Stress-induced changes in gut bacteria, or gut microbiota, may play a significant part in the possible link between exposure to stress and the risk of autoimmune disorders such as multiple sclerosis (MS), a mouse research study says.

In the study “Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells,” researchers showed that social stress changes the gut microbiota of mice, and the genes that are active, triggering the expansion of self-reacting immune cells. This suggests that the onset of stress increases the likelihood that the body would attack itself.

The study, published in the journal mSystems, also noted that some of the bacteria growing in the mice in response to stress have been found in unusually high numbers in the guts of people with MS.

Autoimmune diseases are believed to arise from a complex interplay between genetic and environmental risk factors, some of which have already been linked to MS. Stressful life events also are thought to predispose people to such disorders — but the chain of events behind this link at the cell and molecular levels is still unclear.

Now, immunologist Orly Avni, PhD, and graduate student Michal Werbner, both of Bar Ilan University in Israel, have worked with other collaborators to investigate how stress could lead to autoimmunity.

“We know that there’s strong crosstalk between the immune system and the microbiota,” Avni said in a press release. According to the researcher, an important step in understanding how stress may lead to autoimmune conditions is to identify the genetic responses of bacteria.

The team therefore studied how gut microbiota changed in response to stress in mice with a genetic susceptibility to autoimmunity, specifically to autoimmune optic neuritis (an inflammation that can damage the optic nerve).

To address the impact of stress, researchers divided the mice into two groups: one was exposed to stress in the form of daily, threatening encounters with other aggressive mouse, while the other group was left alone.

After 10 days, researchers found that the stressed mice had higher levels of certain types of bacteria in their gut, including those from the genus Bilophila and Dehalobacterium. These types of bacteria were reported to be highly abundant in the guts of MS patients, as compared with healthy people.

Next-generation sequencing revealed that stress led to the activation of bacterial genes related to virulence — traits potentially harmful for the host, including bacterial growth, motility, and signals sent between bacteria and host.

Bacteria that had turned on these genes in response to stress — which the scientists called “stressed-responsive bacteria” — traveled to the mesenteric lymph nodes, which drain the gut lymph (body fluid containing white blood cells, and a mixture of fats and proteins from the intestine). There, these stressed-responsive bacteria triggered an immune response resembling that found in subjects with an autoimmune disease.

There also was a higher percentage of effector T-cells, termed effector T helper (Th) cells, which are known to play a role in autoimmunity.

“In light of their strategic position in the immune response, when their function is dysregulated, Th cells may initiate or promote a variety of autoimmune diseases; Th1 and Th17 responses dominate many autoimmune diseases, including MS,” the researchers said.

Together, the findings suggested that stress can change the activity of the gut microbiota, which in turn enforces an immune response with the potential to trigger an attack against the body. That increases the risk for autoimmune diseases in susceptible individuals. In other words, stress can promote a response than endangers self-tolerance, which is the capacity of people’s immune systems to avoid attacks onto their own cells and molecules.

However, Avni noted that scientists still lack a deeper understanding of the long-lasting interaction between bacteria and their hosts.

“It’s not enough to study the composition, or the increase or decrease of a species,” she said. “We also have to understand how the microbiota sense us, and how they change their ‘behavior’ accordingly.”

Knowing that may enlighten the way to find tailored microbial interventions that could lessen autoimmune responses and other stress-inducible illnesses.