What are the recommended interventions for modifying the microbiome in individuals with specific conditions, such as Clostridioides (C. difficile) infection?

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Last updated: June 7, 2025View editorial policy

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From the Guidelines

For individuals with Clostridioides difficile infection, the primary recommended intervention is fecal microbiota transplantation (FMT) after standard antibiotic therapy has failed, with a suggested approach of treating with vancomycin 125 mg orally four times daily for 10-14 days, followed by FMT if the infection recurs, as recommended by the AGA and supported by recent guidelines 1. The standard approach for FMT involves delivering the transplant via colonoscopy, with a success rate of 80-90% after a single treatment, and donor stool is screened extensively for pathogens and processed in specialized facilities.

  • Key considerations for FMT in C. difficile infection include:
    • Treating with antibiotics for at least 10 days before FMT, as recommended by the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines 1
    • Ensuring proper donor screening to minimize the risk of pathogen transmission, particularly in the context of the COVID-19 pandemic 1
    • Considering FMT for patients with recurrent or refractory C. difficile infection, with a focus on timing of administration and optimizing donor screening 1
  • Other microbiome interventions, such as probiotics and dietary modifications, may be used as adjunctive therapy, but with more modest benefits, and the narrow-spectrum antibiotic fidaxomicin may be preferred for prevention in high-risk individuals due to its reduced disruption to the gut microbiome 1. The AGA suggests the use of conventional fecal microbiota transplant over no fecal microbiota transplant in adults hospitalized with severe or fulminant C. difficile infection not responding to antimicrobial therapy, with a conditional recommendation and very low certainty of evidence 1.

From the Research

Recommended Interventions for Modifying the Microbiome

The recommended interventions for modifying the microbiome in individuals with specific conditions, such as Clostridioides (C. difficile) infection, include:

  • Fecal microbiota transplantation (FMT) as an early treatment modality to prevent complications and reduce related morbidity and mortality 2
  • Probiotics for secondary prevention in patients with recurrent C. difficile infection, although guidelines acknowledge the lack of compelling evidence 3
  • Microbiome-based interventions, such as nutritional approaches, phage therapy, probiotics, and prebiotics, to modulate gut ecology and the immune system 4

Fecal Microbiota Transplantation (FMT)

FMT has been shown to be effective in reducing C. difficile infection-associated morbidity and mortality, with a cure rate of 76% at week 1 and 55% at week 8 5. Repeated FMT treatments can lead to an overall cure of C. difficile-associated diarrhea (CDAD) in 79% of patients 5. However, questions remain regarding the route of administration, timing, safety, availability, and number of sittings required for FMT 2.

Mechanisms and Pharmacology of FMT

The mechanisms by which FMT cures C. difficile infection are complex and involve the restoration of gut microbiota 6. FMT has been proposed as a method for restoring gut microbiota and has been shown to significantly increase the rate of cure in patients with recurrent C. difficile infection 3. However, the optimal delivery method, sample preparation, and donor selection remain unclear 3.

Real-World Effectiveness of FMT

A real-world clinical study demonstrated the effectiveness of FMT for first or second C. difficile infection, with a cure rate of 76% at week 1 and 55% at week 8 5. The study suggested that forwarding FMT in C. difficile treatment guidelines could improve patient survival 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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