Investigation of Enterococcus Colonisation Impact on Clostridioides difficile Disease Severity - European Medical Journal

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Investigation of Enterococcus Colonisation Impact on Clostridioides difficile Disease Severity

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Microbiology & Infectious Diseases
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Authors:
Alexander Mai , 1 Adelaide Horvath , 1 Khurshida Begum , 1 Thomas Horvath , 1-3 Kevin Garey , 1 * Taryn Eubank 1
  • 1. Department of Pharmacy Practice and Translation Research, College of Pharmacy, University of Houston, Texas, USA
  • 2. Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
  • 3. Texas Children’s Microbiome Center, Department of Pathology, Texas Children’s Hospital, Houston, USA
*Correspondence to [email protected]
Disclosure:

This project was funded by an SIDP Early Career Investigator Grant and ACCP Foundation Junior Investigator Research Award, with payment to the institution. Mai has received support for the present manuscript through the UH SURF Award and UH PURS Award (stipend to support tuition during research), with payment to the author. Garey has received research grants from Acurx Pharmaceuticals and Paratek Pharmaceuticals, with payment to the institution. Horvath T. has received support for the present manuscript via an NIH ORIP S10 Shared Instrument grant, with payment to the institution; a Wellcome LEAP FORM grant and a Wellcome LEAP 1KD grant, with payment to the institution; honoraria from Cell Press STAR Protocols for service to the journal as an associate academic editor; equipment (LC/MS system) from Revvity for the duration of the validation experiments; and served as an Editorial Advisory Board Member for STAR Protocols. The other authors have declared no conflicts of interest.

Citation:
EMJ Microbiol Infect Dis. ;7[1]:48-49. https://doi.org/10.33590/emjmicrobiolinfectdis/ACXJ6776.
Keywords:
Clostridioides difficile, Enterococcus, microbiome.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

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.

References
Mai A et al. Investigation of Enterococcus colonization impact on Clostridioides difficile disease severity. Poster E0154. ESCMID Global, April 17-21, 2026. Bosnjak M et al. Multi-omics analysis of hospital-acquired diarrhoeal patients reveals biomarkers of enterococcal proliferation and Clostridioides difficile infection. Nat Commun. 2023;14(1):7737. Berkell M et al. Microbiota-based markers predictive of development of Clostridioides difficile infection. Nat Commun. 2021;12(1):2241. Smith AB et al. Enterococci enhance Clostridioides difficile pathogenesis. Nature.2022;611(7937):780-6. McDonald LC et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-48.

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