Celiac Patients Have Elevated Risk of Developing C. difficile Infection

Patients with celiac disease have a higher incidence of Clostridioides (formerly Clostridium) difficile infection than the general population, even after accounting for traditional risk factors for developing the sometimes life-threatening diarrheal infection. So found a large database study that its authors say is the first in the United States to determine this association, drawing attention to the need for clinicians to consider the diagnosis for celiac patients with new or recurring diarrhea.

Results of the study conducted by a team of Cleveland Clinic researchers were presented at two meetings in October 2022: the American College of Gastroenterology annual meeting and the International Celiac Disease Symposium.

“Because of this study’s findings, I now test all celiac patients who have persistent diarrhea while following a gluten-free diet,” says lead study investigator Alberto Rubio Tapia, MD, a gastroenterologist and Director of Cleveland Clinic’s Celiac Disease Program. “Testing is simple and quick, and appropriate treatment can help prevent prolonged symptoms, colectomy and even death.”

Methodology and findings

The study investigators searched electronic health record data using Explorys (a platform originally developed by Cleveland Clinic and now part of IBM Watson Health) from 2017 to 2022. Data were obtained from 26 major healthcare systems in the U.S.: 90,060 adult patients with celiac disease and 25,807,720 without celiac disease (controls) were identified.

Key findings:

• A new diagnosis of C. difficile infection occurred in 1.31% (n = 1,180) of patients with celiac disease vs. 0.35% (n = 92,330) of controls (odds ratio 3.69 [95% confidence interval 3.49-3.91]; p< 0.0001).
• After controlling for multiple common risk factors of C. difficile infection (including older age, female gender, white race, presence of inflammatory bowel disease and use of antibiotics or acid-suppressive therapy), multivariate analysis found the odds ratio of celiac patients developing C. difficile compared with controls was 1.34 (95% CI 1.2-1.4); p < 0.0001).
• Treatment outcomes for C. difficile infection (most often using vancomycin and less commonly metronidazole) were comparable between patients with celiac disease and controls.
• Rates of complications (colectomy, sepsis or death within 60 days of C. difficile diagnosis) were low and comparable between the two groups. Colectomy in patients with a history of inflammatory bowel disease, ischemic colitis or neoplasia of the colon were excluded from this analysis.

Key takeaways

Dr. Rubio Tapia notes that this is the largest study to date examining the connection between C. difficile and celiac disease, strengthening its findings. Although the association is modest after controlling for risk factors, he adds, it is important for doctors to keep in mind due to the seriousness of untreated C. difficile infection.

He highlights the following major takeaways:

• C. difficile infection is more likely to occur in patients with celiac disease.
• Elevated risk is still evident beyond what is expected with traditional risk factors.
• Conventional antibiotic therapy for C. difficile infection is as effective in patients with celiac disease as in the general population.
• C. difficile should be added to the differential diagnosis of recurring or persistent diarrhea in celiac patients who are following a gluten-free diet.

“Knowing that celiac patients have a propensity to develop C. difficile infection and that treatment is highly effective, the big mistake would be not to look for it with unexplained diarrhea,” emphasizes Dr. Rubio Tapia.

Possible role of gut microbiome

Why patients with celiac disease have increased susceptibility to C. difficile infection is still an open question, according to Dr. Rubio Tapia. That celiac patients tend to be older, female and white, frequently use antibiotics and acid suppressive therapy, and are likelier to have inflammatory bowel disease, all contribute to the higher rates, he notes. But he suspects that gut microbiome balance may be different in patients with celiac disease, possibly explaining the increased risk beyond those factors.

“Our group is examining how the microbiome in patients with celiac disease may differ from healthy controls and the possible impacts of a gluten-free diet on the microbiome,” he says.