How stress can affect the gut microbiota and cause flare-ups

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New research in mice sheds light on a possible mechanism by which stress can cause flares in Crohn’s disease. Ana Luz Crespi / Stocksy
  • Researchers studied the impact of psychological stress on Crohn’s disease in a mouse model.
  • Psychological stress in mice caused an increase in adherent-invasives E. coli (AIEC) in the intestine.
  • Stress also eliminated the cells that make IL-22, a protein that protects the intestinal lining and can prevent Crohn’s flare-ups.
  • The researchers believe their study could lead to the development of new treatments, including treatment with IL-22, a narrow-spectrum antibiotic, or both.

In recent years, a lot of research has been done on stress and its effects on human health. Scientists have found that stress increases the risk of stroke, Alzheimer’s disease, and diabetes. It can also negatively affect the gut, causing problems like constipation.

Today, a team of researchers from McMaster University in Ontario, Canada, discovered a link between psychological stress and Crohn’s disease.

Using a rodent model, the team observed how stress increased bacteria, such as E. coli, in the intestine and also negatively affected a cytokine which helps protect the intestinal lining from invading bacteria.

Bacteria, such as E. coli, getting into the gut can cause Crohn’s flare-ups.

The study appears in the journal Nature Communication.

Crohn’s disease is an autoimmune disease that causes inflammation of the gastrointestinal tract. The gastrointestinal tract includes everything a person’s body needs to eat, digest, and expel food and waste. It includes the mouth, stomach, intestines and rectum.

Crohn’s disease is one of two types of inflammatory bowel disease (IBD). It’s a chronic disease The most common in North America and Western Europe, affecting approximately 100 to 300 people per 100,000 people.

Symptoms of Crohn’s disease include:

  • diarrhea
  • constipation
  • loss of appetite
  • weightloss
  • swelling of the joints
  • tired
  • skin complications

Treatments for Crohn’s disease include medication, diet changes, and possible surgery to repair damaged sections of the gastrointestinal tract.

Causes for Crohn’s disease are not fully understood. Researchers believe that genetic, hereditary and environmental components may play a role in the disease. And while stress doesn’t cause Crohn’s disease, past research shows that it can affect IBD and Crohn’s disease.

According to Dr Brian Coombes, senior author, professor, and chair of biochemistry and biomedical sciences at McMaster University, many people with Crohn’s disease report experiencing episodes of psychological stress that precede inflammatory flare-ups or increased disease activity .

Examples of psychological stress include relationship problems, the death of a loved one, financial problems, moving, or problems with work.

“We wanted to better understand the link between the brain and the gut that could be the source of this link between stress and poor gut health outcomes,” he told Medical News Today.

“Initially, we focused on the impact of stress on the makeup of the gut microbiome, which led us to a new discovery about how stress negatively impacts our body’s immune system, thereby hampering our ability to repel bacteria associated with disease. ”

– Dr Coombes

For the study, Dr. Coombes’ team used a preclinical mouse model. The researchers used “overnight restraint” as a psychological stressor in a group of mice and deprived a matched control group of animals of food and water for 16 hours.

Mice in the physiological stress group showed an increase in Enterobacteriaceae – a large family of bacteria, including E. coli, that previous research has linked to the IBD.

From there, the researchers gave the mice AIEC, and they again deprived them of food and water or gave them restraining stress during the night. The team found that the amount of AIEC in rodents under stress stress overnight increased significantly, while that in the food deprivation group did not change.

The researchers continued their experiment for 1 month. They applied weekly psychological stress applications to mice, finding that continued psychological stress caused a “marked expansion” of AIEC in the rodent gut.

And as part of the study of the AIEC rodent model, the research team also found stress hormones killed by CD45+CD90+ cells that help make IL-22 – a cytokine which helps to ensure the normal functioning of the cells of the intestinal wall.

If IL-22 production stops, bacteria, such as AIEC, can enter the intestine, causing a Crohn’s flare.

Dr Coombes and his team found that giving mice in their model external treatment with IL-22 helped correct stress hormone damage to intestinal tissue and prevent AIEC from developing. .

Dr. Coombes believes the results of this study could help develop new treatments for Crohn’s disease. For example, treatment with IL-22 could be an avenue that researchers are exploring further through clinical trials, which he said other groups are already leading.

“We also found that stress allows bacteria associated with Crohn’s disease to grow in the gut,” he added.

“Knowing this, if a narrow spectrum antibiotic could be found that selectively inhibits these disease associated bacteria, it could also be of benefit to patients.”

Dr Gérard Honig, director of research innovation for the Crohn’s and Colitis Foundation, said MNT this study allowed researchers to establish a new mechanical link between psychological stress, nutritional status and the growth of AIEC – a well-studied type of bacteria that contributes to inflammation in many people with the disease by Crohn’s.

“Although the link between AIEC and stress-induced colitis will need to be validated in patients before drawing any clinically relevant conclusions, there are many potential implications, which merit further study,” explained Dr Honig. .

“First, Crohn’s patients with ACEI and / or other biological features identified in this work, such as altered IL-22 signaling, may be at particularly high risk for stress-related relapses, and behavioral health interventions could therefore be a priority in this patient. segment.”

“Second, many clinical-stage investigational therapies are already in development targeting the factors studied here, including IL-22 and AIEC colonization, which could be particularly beneficial in patients at high risk of exacerbation. of stress-related illness. “

For the next steps in his research, Dr Coombes said they plan to explore how quickly the gut microbiota recovers after stress and if there are any long-term consequences. “We would also like to explore corrective therapies, such as IL-22 and narrow spectrum antibiotics, (alone) or in combination, to see how this helps resolve disease activity in the gut.”

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