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

Over the past few years, there has been much research surrounding stress and its effects on human health. Scientists have found that stress increases the risk for stroke, Alzheimer’s disease, and diabetes. It can also adversely affect the gut, causing problems such as constipation.

Now, a team of researchers from McMaster University in Ontario, Canada, has found a connection between psychological stress and Crohn’s disease.

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

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

The study appears in the journal Nature Communications.

Crohn’s disease is an autoimmune disease that causes inflammation of the gastrointestinal tract. The gastrointestinal tract includes everything a person’s body requires for eating, digesting, and expelling food and waste. It comprises the mouth, stomach, intestines, and rectum.

Crohn’s disease is one of two types of inflammatory bowel disease (IBD). It is a chronic condition most common in North America and western Europe, affecting about 100–300 for every 100,000 people.

Symptoms of Crohn’s disease include:

  • diarrhea
  • constipation
  • loss of appetite
  • weight loss
  • swollen joints
  • tiredness
  • skin complications

Treatments for Crohn’s include medications, diet modifications, and possible surgery to fix any damaged sections of the gastrointestinal tract.

Causes for Crohn’s disease are not completely known. Researchers believe genetic, hereditary, and environmental components may play a part in the condition. And while stress does not cause Crohn’s, past research shows 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 individuals with Crohn’s disease report feeling episodes of psychological stress that precede inflammatory flares or increased disease activity.

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

“We were interested to better understand the connection between brain and gut that might be driving this connection between stress and poor health outcomes in the gut,” he explained to Medical News Today.

“Our focus was initially on how stress impacted the make-up of the gut microbiome, which led us to a new discovery into how stress negatively impacts our body’s immune system, thereby hampering our ability to ward off disease-associated bacteria.”

– Dr. Coombes

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

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

From there, researchers gave the mice AIEC, and they once again either deprived them of food and water or administered overnight restraint stress. The team found the amount of AIEC in the rodents subjected to overnight restraint stress increased significantly, while that of the food deprivation group did not change.

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

And within the study of the AIEC rodent model, the research team also found stress hormones killed off CD45+CD90+ cells that help make IL-22 — a cytokine that helps ensure the cells of the gut wall function normally.

If IL-22 production halts, then bacteria, such as AIEC, can get into the gut, causing a Crohn’s flare-up.

Dr. Coombes and his team found that giving mice in their model an external IL-22 treatment helped correct the damage that stress hormones caused to gut tissues and keep AIEC from expanding.

Dr. Coombes believes the outcomes of this study may help lead to the development of new treatments for Crohn’s disease. For example, IL-22 treatment might be one avenue that researchers further explore through clinical trials, which he said other groups are already conducting.

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

“Knowing this, if one could find a narrow-spectrum antibiotic that selectively inhibits these disease-associated bacteria, that might have benefit for patients as well.”

Dr. Gerard Honig, director of research innovation for the Crohn’s & Colitis Foundation, told MNT this study has allowed researchers to establish a novel mechanistic link between psychological stress, nutritional state, and the growth of AIEC — a well-studied type of bacteria thought to contribute to inflammation in many people with Crohn’s.

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

“First, Crohn’s patients carrying AIEC, and/or other biological characteristics identified in this work, such as altered IL-22 signaling, could be at particularly high risk of stress-related flares, and thus behavioral health interventions could be prioritized within this patient segment.”

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

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