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Engineering probiotics to inhibit *Clostridioides difficile* infection by dynamic regulation of intestinal metabolism

Medicine and Health

Engineering probiotics to inhibit *Clostridioides difficile* infection by dynamic regulation of intestinal metabolism

E. Koh, I. Y. Hwang, et al.

This groundbreaking research by Elvin Koh, In Young Hwang, Hui Ling Lee, Ryan De Sotto, Jonathan Wei Jie Lee, Yung Seng Lee, John C. March, and Matthew Wook Chang unveils a novel therapeutic strategy targeting *Clostridioides difficile* infection through engineered probiotics. These innovative probiotics restore bile salt metabolism, effectively combating CDI and improving survival rates in mice, showcasing the powerful potential of microbiome modulation.

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Playback language: English
Abstract
This study investigates the role of dysregulated microbiome-mediated bile salt metabolism in *Clostridioides difficile* infection (CDI) and explores a novel therapeutic strategy. Engineered probiotics with a genetic circuit (sensor, amplifier, actuator) were designed to restore bile salt metabolism. These probiotics effectively limited *C. difficile* spore germination and vegetative cell growth in vitro and significantly reduced CDI in a mouse model, resulting in 100% survival and improved clinical outcomes. This approach highlights the potential of microbiome modulation to target the host-pathogen microenvironment for CDI treatment.
Publisher
NATURE COMMUNICATIONS
Published On
Jul 04, 2022
Authors
Elvin Koh, In Young Hwang, Hui Ling Lee, Ryan De Sotto, Jonathan Wei Jie Lee, Yung Seng Lee, John C. March, Matthew Wook Chang
Tags
Clostridioides difficile
probiotics
bile salt metabolism
microbiome
infection
therapeutic strategy
CDI

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