Crohn’s disease is an inflammatory disease of the gastrointestinal tract triggered by microbial and environmental insults. The global burden of disease associated with CD is rising, particularly in developed countries where incidence has been increasing for decades.
Current standards of care, including immunomodulatory biologics, are expensive and have high rates of primary and secondary non-responsiveness. Thus, there is an urgent unmet clinical need to better understand the microbial and environmental triggers of CD that will underpin new preventions and therapies.
Some changes that are commonly seen in CD microbiome include decreased community diversity, reduced levels of Clostridiales and increased abundance of Proteobacterias. Also, they have shown bacteria in close association with the mucosal epithelium in CD patients, particularly members of the Enterobacteriaceae that are enriched in virulence and secretion pathways.
Many components of the mucosal immunity are altered in CD. These changes include epithelial barrier integrity, mucous production and cell turnover. All of these elements of mucosal immunity work to restrict bacteria to the gut lumen and to reduce the overgrowth of pathogens.
One type of cytokine, Interleukin (IL)-22 regulates several aspects of mucosal immunity in the gut, including the production of AMPs and activation of nutritional immunity.
New Study Results
A team of researchers from the McMaster University in Ontario, Canada has found a connection between psychological stress and Cronh’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, IL-22 that helps protect the gut lining from invading bacteria.
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 Cronh’s disease.
The team used a preclinical mouse model, utilizing “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 psychological stress group showed an increase in Enterobacteriaceae, a large family of bacteria that includes E. coli, that previous research has linked to IBD.
From there, researchers gave the mice Adherent-invasive E. coli (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.
They continued the experiment for 1 month, doing weekly applications of psychological stress to the mice, finding a marked expansion of AIEC throughout the gut of the rodents.
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.
The researchers believe that their study may lead to the development of new treatments, including an IL-22 treatment, narrow-spectrum antibiotic or both for Crohn’s disease.
Shaler, C.R., Parco, A.A., Elhenawy, W. et al. Psychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts. Nat Commun 12, 6664 (2021). https://doi.org/10.1038/s41467-021-26992-4
Corrie Pelc. (2021, Nov 24). Crohn’s: How stress may increase disease-associated bacteria, causing flare-ups. Medical News Today. Retrieved from: