Topic: C. Difficile

This study sought to characterize the bacterial and fungal microbiota changes associated with Clostridium difficile infection (CDI) among inpatients with diarrhea, in order to further explain the pathogenesis of this infection as well as to potentially guide new CDI therapies. Twenty-four inpatients with diarrhea were enrolled, 12 of whom had CDI. Each patient underwent stool testing for CDI prior to being treated with difficile-directed antibiotics, when appropriate. Clinical data was obtained from the medical record, while each stool sample underwent 16S rRNA and ITS sequencing for bacterial and fungal elements. An analysis of microbial community structures distinct to the CDI population was also performed. The results demonstrated no difference between the CDI and non-CDI cohorts with respect to any previously reported CDI risk factors.
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Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were either not antibiotic treated or treated with metronidazole, vancomycin, or fidaxomicin, the three most common CDI therapies.
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Novel culture independent technologies have further elucidated the composition of the human mycobiome, though the role of fungi in human health and disease remains largely unknown. Recent studies have suggested conflicting roles for fungi in the gastrointestinal tract, underscoring the complexity of the interactions between the mycobiome, its bacterial counterpart, and the host. One key example is the observation that fungal taxa are overrepresented in patients with Clostridioides difficile infection (CDI), suggesting a role for fungi in this disease. Recent studies in murine models have demonstrated the ability of the commensal fungus Candida albicans to alter the course of CDI, supporting the notion that fungi play a role in this infection.
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There has been no prior application of matched metagenomics and meta-transcriptomics in Clostridioides difficile infection (CDI) evaluating the role of fungi in CDI or identifying community functions that contribute to the development of this disease. We collected diarrheal stools from inpatients and utilized a tiered sequencing approach 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. Distinct bacterial and fungal compositions distinguished CDI-positive and -negative patients, with the greatest differentiation between the cohorts observed based on bacterial metatranscriptomics. Bipartite network analyses demonstrated that Aspergillus and Penicillium taxa shared a strong positive relationship in CDI patients and together formed negative co-occurring relationships with several bacterial taxa.
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