Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives

Abstract

Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.

The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome

“…[ 160,161 ] Of note, bacteriophages rely on bacteria as hosts to function. [ 164,165 ] They can either destroy the bacteria (virulent or lysogenic phages) or modify their behavior (lysogenic phages), including drug resistance and virulence. These phages show promise in combating pathogen‐led diseases like CDI and antibiotic‐resistant bacterial infections.…”

A tale of two phage tails: Engineering the host range of bacteriophages infectingClostridioides difficile

“…Paradoxically, the first-line therapy for CDI is antibiotic treatment 6 . The continued long-term use of antibiotic therapy may lead to reduced susceptibility of the bacterium to antimicrobials and further instigate emergence of resistant and hypervirulent strains 7,8 . The nature of CDI calls for a more targeted treatment with precise therapies that leave the microbiome unperturbed.…”