BACKGROUND AND AIMSEnterococcus colonisation with Enterococcus faecalis and Enterococcus faecium is a known risk factor for Clostridioides difficile infection (CDI).1-3 Enterococcus co-colonisation increases C. difficile virulence and toxin production through cross-feeding.4 However, current disease severity definitions do not take into account the patients’ microbiota.
This study aimed to investigate the impact of Enterococcus colonisation on disease severity.
The group with severe disease had a higher percentage of patients categorised as having high Enterococcus spp.
colonisation trends with IDSA disease severity, it is highly possible that other microbiota members cross-feed with C. difficile.
colonisation and CDI disease severity, it is highly likely that other microorganisms contribute to this association.
BACKGROUND AND AIMS
Enterococcus colonisation with Enterococcus faecalis and Enterococcus faecium is a known risk factor for Clostridioides difficile infection (CDI).1-3 Enterococcus co-colonisation increases C. difficile virulence and toxin production through cross-feeding.4 However, current disease severity definitions do not take into account the patients’ microbiota. This study aimed to investigate the impact of Enterococcus colonisation on disease severity.
MATERIALS AND METHODS
This was a case-control study of adult patients hospitalised with CDI from two health systems (14 hospitals) in Houston, Texas, USA (2016–2025). Patients with severe CDI were matched to non-severe patients (1:1) on age ±10 years and immunocompromised status. Stool samples were collected from hospitalised patients with CDI, and stool underwent DNA extraction for quantitative PCR of E. faecalis and E. faecium. Metabolomics were completed by liquid chromatography-tandem mass spectrometry. Disease severity and CDI classification were defined according to the 2017 Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA)clinical guidelines.5
RESULTS
A total of 190 patients (95 matches) with CDI were included (female: 54.7%; age >65 years: 60%; hospital-acquired CDI: 42%; CDI initial episode: 87%). Patients with Enterococcus spp. quantity >106 were designated as high colonisation; 61% of patients were highly colonised. The group with severe disease had a higher percentage of patients categorised as having high Enterococcus spp. colonisation, though not statistically significant (67.5% versus 58.7%; p=0.07). While high Enterococcus spp. colonisation trends with IDSA disease severity, it is highly possible that other microbiota members cross-feed with C. difficile. Metabolomics completed on 84 matches with sufficient stool showed that patients with severe disease had significantly higher amounts of ornithine in the stool than patients with non-severe disease (6,739 ng/mL versus 4,270 ng/mL; p=0.02).
CONCLUSION
The gut microbiota is a diverse environment with many inter-species interactions. While a trend is observed between Enterococcus spp. colonisation and CDI disease severity, it is highly likely that other microorganisms contribute to this association. Future metagenomic and metabolomic analysis is warranted.
