Key Differences Found in Microbiomes of Patients

Scientists have identified possible biomarkers that may make it easier to distinguish patients with Clostridioides difficile infection (CDI) from those with diarrhea from other causes.

Writing in the journal Frontiers in Cellular and Infection Microbiology, corresponding author Silvia Vázquez-Cuesta, PhD, of the Complutense University of Madrid, and colleagues, noted that there are a number of known risk factors for CDI, including advanced age, hospital stays, and treatment with proton pump inhibitors or antibiotics. However, given the significant health and economic burden associated with the disease, the authors said better strategies are needed to help prevent CDI in the first place. One possible first step toward prevention, they said, is better understanding differences in the gut microbiota of patients with CDI, healthy controls, and patients with diarrhea from causes unrelated to CDI.

Such knowledge, “could help us predict which patients are at immediate risk of CDI, which will progress better or worse, and which will experience recurrence of CDI.”

Another challenge, they said, is distinguishing between patients who are colonized with C difficile and those with infections.

The authors decided to analyze clinical data and fecal samples from study participants in 5 different groups: patients with CDI, patients with recurrent CDI, patients with non-CDI diarrhea, patients with C difficile colonization, and healthy controls. A total of 753 samples were collected between 2018 and 2021, representing 657 total participants. The largest proportion of samples (324) were from patients with non-CDI diarrhea; the next largest cohort of samples (247) were from patients with CDI.

The analysis found significant differences between groups in terms of alpha and beta diversity, and in terms of taxonomic abundance. They found that the genera Bacteroides, Proteus, Paraprevotella, and Robinsoniella, were significantly associated with CDI, while the genera Veillonella, Fusobacterium, Lactobacillus, and Clostridium sensu stricto I, appeared to be biomarkers for recurrent CDI. Meanwhile, Parabacteroides, Faecalicoccus, Flavonifractor, and Clostridium XVIII were closely associated with C difficile colonization.

“The comparison with healthy individuals revealed a considerable difference in the state of the intestinal microbiota compared with patients with gastrointestinal disorders, whether due to C difficile or not, namely, greater richness, alpha diversity, and evenness,” Vázquez-Cuesta and colleagues wrote. “These differences are also evident in beta diversity, where the healthy individuals group differs significantly from all the others.”

The investigators also said that, in contrast to previous studies, their data showed differences in the alpha diversity and richness between the CDI group and the non-CDI diarrhea group. They said previous studies that found no such differences were based on smaller sample sizes. These findings underscore the importance of having a large number of people in each cohort of such studies, they added.

Consistent with earlier research, they found that alpha and beta diversity correlated with specific CDI risk factors, such as recent antibiotic treatment and previous episodes of CDI.

Vázquez-Cuesta and colleagues said they believe this is the first study to look so broadly at biomarkers and for such a wide array of subgroups. Most of the previous research, they said, focused on distinguishing between 2 groups, such as those with CDI and those with recurrent CDI.

The investigators cautioned that further study is warranted, but they said the insights yielded by their investigation ought to make it easier to differentiate between CDI and related conditions.

“Our approach will enable us to further improve the diagnosis, management, and treatment of CDI,” they said.