New preclinical research suggests that bowel preparation procedures for colonoscopies may temporarily alter gut balance, culminating in unappreciated effects in patients with compromised gastrointestinal health.

The study, published in Cell Reports Medicine, found that simulating bowel preparation in mouse models disrupted the gut environment, making the mice more susceptible to infection and inflammation.

"Colonoscopies play a crucial role in the diagnosis and treatment of gastrointestinal pathologies, including cancer, so it’s important to emphasize that we’re not trying to scare anyone away from doing bowel preparation for a colonoscopy," said Dr. Carolina Tropini, a professor in the Department of Microbiology and Immunology and the School of Biomedical Engineering at the University of British Columbia (UBC) and senior author of the study.

"But with further studies in humans, we hope to understand whether there are situations in which, for specific patients, these procedures may put them at risk of disease exacerbation.”

The findings could help guide strategies to make colonoscopies safer for people with inflammatory bowel disease (IBD), who undergo the procedure more frequently than the general population.

Before a colonoscopy, the patient ingests a laxative solution to clean out the intestinal contents, allowing the doctor to insert a probe and get a clear picture of the health of the lower digestive tract. But for some, bowel preparation amounts to more than just one unpleasant evening spent in the bathroom.

In previous work with Dr. Sidhartha Sinha’s lab at Stanford University, Dr. Tropini’s team found that people with IBD were more likely to be prescribed anti-inflammatory steroids in the weeks following bowel preparation, hinting at the phenomenon of post-procedure flare-ups.

In the new study, the researchers administered to mice a solution of polyethylene glycol (PEG), the active ingredient in laxatives used in bowel preparation. PEG triggered diarrhea in the mice, temporarily depleting the protective mucus barrier that lines the gastrointestinal tract as well as the beneficial bacteria that reside in the gut. The treatment also reduced the levels of short-chain fatty acids—small molecules that gut bacteria produce to help fight infection and inflammation.

While the mice recovered their healthy state within a few days, bowel preparation appeared to create a window of weakened defenses against pathogens. To explore this, the researchers administered either the PEG laxative solution or water to mice and then exposed them to Salmonella Typhimurium, a model infectious bacterium. In the water treatment group, there were no signs of Salmonella Typhimurium infection, but in the PEG treatment group, the bacterium bloomed inside the gut and spread to the lymph nodes, spleen and liver.

The team next investigated how pathogens might exploit the unique conditions of bowel preparation to expand in the context of IBD. As part of their community of gut microorganisms, people with IBD often harbor pathobionts—bacteria that are usually benign, but can act as pathogens in a disrupted environment.

To mimic the scenario in which a patient receives a colonoscopy shortly after a period of inflammation, the researchers colonized mice with gut microorganism samples from two people with ulcerative colitis, a type of IBD. They treated the mice with a chemical that induces inflammation and then performed the bowel preparation procedure on a portion of the rodents.

While the control group quickly recovered from the chemical inflammation treatment, the bowel preparation group showed a short-term increase in inflammatory disease activity and gastrointestinal tissue changes. The bowel preparation cohort also displayed higher levels of IBD-associated pathobionts, which have been linked to worsened inflammation, in organs outside of the gut.

The findings warrant clinical studies into the risks of bowel preparation for vulnerable patient populations. The team is now collaborating with Dr. Genelle Lunken’s lab at the BC Children’s Hospital Research Institute to collect survey information from people undergoing colonoscopies to generate more rigorous data on the potential for IBD symptom exacerbation following the procedure.

If the results are validated in humans, “We can use our model to look into ways to make bowel preparation safer for people with IBD,” Dr. Tropini said. For example, tweaking the laxative formulation or co-administering beneficial gut bacteria, short-chain fatty acids or agents that preserve the mucus lining might help mitigate adverse effects, enabling safe and effective colonoscopies.