Predicting C Difficile with 5 Key Factors

Vanessa L. Hale, MAT, DVM, PhD

Five key risk factors can be used to predict the patients most susceptible to Clostridium difficile (C difficile) infection, according to recent findings.

Investigators from the Mayo Clinic in Rochester, Minnesota, examined the altered microbial community (known as dysbiosis) in C difficile patients and mice models in order to determine the risk factors for infection onset.

The study authors noted that while some C difficile patients displayed dysbiosis, that is not the case for all C difficile patients. To further evaluate dysbiotic conditions, mice models were used in similar research projects. Using germ-free mice is another alternative, which researchers believe can more faithfully replicate the structure and function of human gut microbial communities.

The researchers identified 115 people with diarrhea but without C difficile infection at baseline, though some of this group went on to develop C difficile infection. The researchers then compared these patients to 118 healthy controls. The investigators then identified 5 contributing factors that they said could help predict which individuals with diarrhea were dysbiotic: current hospitalization, recent hospitalization (within the last 4 weeks), recent antibiotics (within the last 3 weeks), immunosuppression, and prior C difficile infection.

“This suggests that clinicians could use these 5 factors (or have an electronic medical record flag patients with these factors) to identify individuals at high-risk for C difficile infection although more validations across different cohorts is needed,” the study’s co-lead author Vanessa L. Hale, MAT, DVM, PhD told MD Magazine®. Hale added that in a retrospective analysis of more than 17,000 patients, these 5 factors could predict future C difficile infections.

About half of the diarrhea patients had gut microbial communities that appeared healthy. However, the remaining patients had very different microbes and different levels of metabolites, which the researchers then categorized as “dysbiotic” or unhealthy.

The investigators also determined that 1 of the reasons a dysbiotic microbial community makes for an especially susceptible patient is because these microbial communities have an abundance of amino acids. Hale added that 1 particular amino acid called proline is plentiful in this environment, which makes it harder for C difficile to multiply in these communities.

“Healthy microbial communities probably have other microbes that efficiently utilize all of the amino acids and proline, leaving very little around for the taking,” Hale said.

In another part of their study, the researchers transplanted dysbiotic human stool into mice and found that the mice were more likely to be infected with C difficile than mice that received healthy human stool.

Later, mice were fed low-protein diets to limit the growth of C difficile, which supported the belief that proline and other amino acids could play a role in infection development. It’s possible, they said, that dietary interventions could reduce the risk for C difficile in patients who are already at-risk due to other factors.

“We determined that we can colonize germ-free mice with a variety of human gut microbial communities — allowing us to better capture the diversity of human microbial communities when evaluating disease processes and susceptibility,” Hale concluded, speaking of “a slightly more academic finding” from the study authors.

“Other studies on C difficile often use conventional mice that undergo antibiotic treatment. While this is an effective model, it can be more homogenous than actual human communities.”

The paper, titled “Clostridioides difficile uses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea,” was published in the journal Science Translational Medicine.