C Diff and Fungi: An Unexpected Partnership

Few gastrointestinal infections drive fear like that of Clostridioides difficile (C diff). A nasty bacterial infection that can cause diarrhea and colitis, it is increasingly associated with antibiotic use and health care exposure. The US Centers for Disease Control and Prevention (CDC) estimates that nearly half a million cases occur each year in the United States and that among patients infected, 20% will experience a recurrence. Moreover, patients over 65 years of age who are diagnosed with C diff related to health care exposure, 1 in 11 will die due to their infection.

This gut bug has become a growing issue for infection prevention efforts in health care settings and combatting its easy spread has challenged efforts across the country. As investigators push to advance C diff response and prevention efforts, part of the challenge is truly understanding how this bacteria works. In a new investigation led by David B. Stewart, MD, FACS, FASCRS, of the University of Arizona, a study team sought to use a new approach to understand the dynamics at play for C diff infections.

By harnessing the power of matched metagenomics and metatranscriptomics, the investigators assessed the role of fungi in C diff infections. Fungi have been frequently overlooked as a potential component to C diff infections and as the threat of antimicrobial resistance grows, it is important to identify those microbial pathways that contribute to infection. First, the investigators collected stool from 49 patients (18 of whom had tested positive for C diff ) and worked to identify “enriched bacterial and fungal taxa, using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing, with matched metagenomics and metatranscriptomics performed on a subset of the population.”

Not surprisingly, there were distinct bacterial and fungal compositions in those patients with and without C diff infections. Interestingly, the investigators uncovered through bipartite network analyses that Aspergillus and Penicillium taxa had a positive relationship in those patients with C diff infections and actually had a “negative co-occurring relationship” with many bacterial taxa, like that of Oscillospira, Microbacteriaceae, and Cytophagaceae.

The researchers emphasized that after finding such strong pathways between those with C diff infections and biofilm production, there is definitely a fungus-associated bacteriome that collaborates with C diff to facilitate inflammation and infection.

These findings are particularly interesting as very little attention has been put on fungal taxa since they make up very little of the microbiome. Given their low profile in the gut, the finding of their interactions and relationship with C diff should be further assessed. The imbalance in the gut that helps facilitate the C diff infection, such as contributory Escherichia coli, emphasizes the complex dynamics within our guts. The unique mixture of bacteria and fungi that are present with C diff infections are an indicator of the complex relationship.

The researchers emphasized the need to further assess the role of fungi in relation to C diff infections where antibiotics played a role. Understanding the dynamics of fungi in C diff interactions is the next step—do they help or hinder? So far, we’ve reached the first step by identifying that an all too forgotten microbe, fungi, plays a role in gut infections that are wreaking havoc across the United States.