New evidence could explain why stress is a risk factor for autoimmune disease. A recent study in mice reveals that persistent social stress changes gut microbiota, or microorganisms, in ways that can trigger certain immune responses.
Autoimmune conditions develop when the immune system attacks the body's own tissues, organs, and cells. It responds to them as though they were disease-causing bacteria and viruses.
Studies have identified stress as a risk factor for autoimmune disease. However, the mechanism of the link is unclear.
Researchers at Bar Ilan University in Israel have now found that gut bacteria in mice respond to social stress by increasing the number of effector T helper cells, immune cells that play a role in autoimmunity.
They report their findings in a recent paper in the journal mSystems.
"We know that there's strong crosstalk between the immune system and the microbiota," says senior study author and immunologist Orly Avni, Ph.D.
Avni and her team found that persistent social stress changed not only the expression of genes in the mice's gut bacteria but also their composition.
"And the consequent immune response to that threat jeopardized the tolerance to self," she adds.
Symptoms vary in autoimmune diseases
In the United States, more than 50 million people have an autoimmune disease, according to an estimate from the American Autoimmune Related Diseases Association.
The causes of many of these diseases, which occur more frequently in women than in men, are not clear.
Aside from inherited risks, scientists suspect that the chances of developing an autoimmune disease arise mainly from complex interactions between genes and the environment.
What makes the investigation into the causes of autoimmune diseases particularly challenging is the varied nature and severity of symptoms. This variety differs not only across conditions but also within them.
MS has unpredictable symptoms that can range from "relatively benign" to "disabling" and even "devastating."
The disease often starts with vision problems and progresses to weakness and difficulties with balance and coordination.
Scleroderma can affect various parts of the body, including internal organs, skin, and blood vessels. The different types of this disease vary by the extent to which the fibrosis is localized or systemic.
Stress alters gut bacteria in mice
In the new study, the researchers used two groups of mice: the social stress group and the control group. They exposed the social stress group to 10 days of daily encounters with other aggressive, dominant mice. The control group, in the meantime, experienced no such encounters.
When they subsequently analyzed the gut microbes of the mice, the investigators found that the social stress group had more Bilophila and Dehalobacterium than the controls.
Scientists have also found higher levels of these gut bacteria in people with MS.
Further investigation revealed that stress had altered some genes in the mice's gut microbes. The most significant gene changes were those that help bacteria to grow, move around, and relay signals to and from their host.
Increasing the expression of these genes in microbes can help them travel outside of the gut. The team found, for instance, that such alterations could allow the microbes to travel to nearby lymph nodes where they could trigger immune responses.
The gut lymph nodes of the stressed mice contained higher levels of not only more pathogenic bacteria but also effector T cells, "including myelin-autoreactive cells."
The findings suggest that there is a chain of events whereby stress exposure, changes to gut bacteria, and changes to immune cells lead to a higher risk of an autoimmune attack.
However, Avni warns that while it appears that gut bacteria can react to social stress, there is still a way to go to find out how these events play out in the longer term.
A better understanding of this complex relationship could, one day, lead to individualized gut microbe treatments for autoimmune conditions that are sensitive to stress.
"It's not enough to study the composition or the increase or decrease of a species. We also have to understand how the microbiota sense us and how they change their 'behavior' accordingly."
Orly Avni, Ph.D.