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Patients with Clostridioides difficile infection had different bacterial and fungal composition in their stool compared with that of uninfected patients, researchers found.

Distinct species of fungus and bacteria were enriched in the group of patients with C. difficile infection, but this was not the case in uninfected patients, reported Regina Lamendella, PhD, of Juniata College in Huntingdon, Pennsylvania, and colleagues.

C. difficile is one of the most common nosocomial infections, and this study suggested that patients with these infections host a mix of bacteria and fungi that's specific to the disease, and which helps the disease resist treatment, the authors said in , a journal of the American Society for Microbiology.

"The development of C. difficile infection is apparently influenced both by bacterial pathogens and fungi particular to this disease," co-author David Stewart, MD, of the University of Arizona College of Medicine in Tucson, said in a statement. "Until now, fungi have been understudied and under-appreciated in the gut microbiome."

Lamendella also said that this discovery was particularly "astounding," because fungal taxa are such a small percentage of organisms in the gut.

The authors noted this was the first published merged-omics data comparing patients with diarrhea, with and without C. difficile infection. They used high throughput sequencing and then conducted bacterial gene expression analyses on stool samples from the patients.

Researchers examined stool samples from 49 patients total -- 18 that tested positive for C. difficile and 31 that tested negative. The C. difficile group tended to be slightly older (mean age about 65), while the uninfected patients were a mean age of about 60. There were no differences in gender, number of chronic comorbidities, or incidence of antibiotic use prior to collection of stool samples in the groups.

They found two fungal species and nine bacterial species that were significantly enriched in the C. difficile cohort, which was notable given the lack of difference in the patients' antibiotic use between the two groups.

"[This] suggests that the enrichment of fungal organisms in [C. difficile infection] is not simply an epiphenomenon caused by antibiotics with fungi coincidentally filling spatial niches left unoccupied by diminished bacterial populations," they wrote. "This finding lends further support to the concept that the dysbiosis associated with [C. difficile infection] has an important contribution from fungal organisms."

Researchers also discovered that increases in fungus were tied to decreases in so-called "helpful" bacteria. Gene expression then uncovered new pathways linked to C. difficile infections that pointed to other bacterial species, such as Escherichia coli, that could potentially contribute to dysbiosis associated with C. difficile infection, the authors said.

However, Lamendella cautioned in a statement that several important questions remain unanswered in regards to what these findings mean for patient care.

"Where we're headed next is to try to pin down the interaction between C. diff and specific fungi, as well as other organisms within the gut," she said. "Is that relationship antagonistic and negative, or positive? Do the fungi actually perpetuate gut dysbiosis?"

Lamendella added that the fungi could potentially be a therapeutic target, and that antifungal drugs might be repurposed to treat C. difficile or other diseases.

The authors said that future studies hope to investigate the role of E. coli and Pseudomonas aeruginosa in C. difficile infection using animal models, as well as whether adding an antifungal therapy to C. difficile-directed antibiotics could improve success of the treatment.

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