Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in Clostridioides...

Area of Science:

• Microbiology and Infectious Diseases
• Gut Microbiome Research
• Fungal-Bacterial Interactions

Background:

• Clostridioides difficile infection (CDI) is a major healthcare-associated bacterial infection.
• The role of fungi and community functions in CDI pathogenesis remains largely unexplored.
• Previous studies have not utilized matched metagenomics and metatranscriptomics for CDI.

Purpose of the Study:

• To investigate the role of fungi in CDI using advanced sequencing techniques.
• To identify microbial community functions contributing to CDI development and persistence.
• To explore transkingdom interactions between bacteria and fungi in CDI.

Main Methods:

• Collected diarrheal stool samples from 49 inpatients (18 with CDI).
• Employed 16S and ITS rRNA gene amplicon sequencing for bacterial and fungal taxa identification.
• Performed matched metagenomics and metatranscriptomics on a subset of samples.

Main Results:

• Distinct bacterial and fungal compositions differentiated CDI-positive and -negative patients.
• Aspergillus and Penicillium showed positive correlation in CDI patients and negative correlation with specific bacteria.
• Metatranscriptomics revealed enriched pathways in CDI related to biofilm production, quorum-sensing, and osmotic regulation.

Conclusions:

• CDI is associated with a distinct fungus-associated bacteriome, highlighting transkingdom interactions.
• Inflammation, osmotic changes, and biofilm production are key elements in CDI pathophysiology.
• Identified antibiotic-independent mechanisms potentially contributing to CDI recurrence and treatment failure.