IBD May Make Patients More Susceptible to Clostridioides difficile, Study Posits

Altered microbiota and inflammation associated with irritable bowel disease (IBD) appear to make it more difficult for patients to fight off Clostridioides difficile infection, according to a recent study.

A new study based on a mouse model suggests people who have irritable bowel disease (IBD) may be more susceptible to Clostridioides difficile (C. diff) infection (CDI).

The study adds more detail to the suspected, but little understood, connection between the 2 conditions. The findings were published in the journal mBio.

An intact intestinal microbiota can confer protection against CDI, but patients who are exposed to antibiotics can experience disruption of the microbiota that causes them to be susceptible to CDI.

The gut microbiota also plays an important role in the development of IBD, noted corresponding author Vincent B. Young, MD, PhD, of the University of Michigan, and colleagues. Patients with more severe microbiota disturbances can be more susceptible to CDI, Young and colleagues noted, a fact reflected in the growing rates of CDI among patients hospitalized for IBD. Patients who receive fecal microbiota transplantation to treat recurring CDI infection tend to see worse outcomes if they have concomitant IBD, they noted.

Both IBD and CDI have been studied extensively in mouse models, but Young and colleagues said the two have not been specifically studied as comorbidities.

“We wished to develop a system where we could evaluate the specific role of intestinal inflammation and gut microbiota in inducing susceptibility to C. difficile colonization and infection,” they explained.

To achieve this, the investigators focused on Heliobacter hepaticus, a bacterium normally present in mouse gut microbiota, but which can lead to pathological distal intestine inflammation in mice that lack intact interleukin 10 (IL-10) signaling. Using such inflammation as a proxy for human IBD, Young and colleagues then examined whether mice with intestinal inflammation were more susceptible to C. diff colonization.

Wild type mice and IL-10-/- mice were given H. hepaticus or sterile broth. The wild-type mice did not develop intestinal inflammation, regardless of whether they had been given the bacterium or the sterile broth. Meanwhile, the cohort of IL-10-/- mice who received H. hepaticus did develop colitis.

Next, the investigators performed a C. diff challenge to ascertain whether the IBD mice were more susceptible to CDI when compared to a control group. Indeed, they were. IL-10-/- mice who had not been exposed to H. hepaticus, on the other hand, proved resistant to C. difficile colonization.

“These studies with a novel mouse model of IBD and CDI emphasize the importance of host responses and alterations of the gut microbiota in susceptibility to C. difficile colonization and infection in the setting of IBD,” Young and colleagues wrote.

Young and colleagues said the association between gut microbiota alterations, inflammation, and CDI susceptibility is complex, but they said their study suggests that changes in the microbiota alone are not enough to weaken the body’s ability to fight off C. diff. Rather, inflammation also appears to play an important role.

“Only when these changes in the microbiota are accompanied by the development of intestinal inflammation is a luminal environment created that is permissible to the establishment of C. difficile colonization,” they said.

Young and colleagues said there are many questions yet to be answered, but they said the format and model used in their study can be used in future research to better understand the complex interplay between the microbiota, IBD, and CDI.

Reference

Abernathy-Close L, Barron MR, George JM, et al. Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection. mBio. 2021;12(3):e0273320. doi:10.1128/mBio.02733-20