To combat the development and effects of Clostridium difficile infection (CDI), researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have developed a probiotic to restore bile salt metabolism, which is present in the digestive tract.
The infectious bacterium Clostridium causes CDI, an infection of the large intestine or colon that results in infectious diarrhoea. The majority of CDI cases have been seen in people who are currently taking antibiotics or have recently finished their course of antibiotics.
Antibiotic medication during CDI treatment results in dysbiosis, an unbalanced gut microbiota that can impair other microbiome functions like bile salt metabolism. When bile salt metabolism is out of balance, dormant Clostridioides difficile spores can become active and cause CDI, severe diarrhoea, colitis, or a reinfection of CDI.
The Synthetic Biology Translational Research Program at NUS Medicine and NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) have developed a probiotic that can detect the occurrence of antibiotic-induced microbiome imbalance and express an enzyme that can regulate the bile salt metabolism upon detection. The research team is led by Associate Professor Matthew Chang. This probiotic incorporates a genetic circuit that consists of a sensor, amplifier, and actuator that are all genetically encoded.
Because of its demonstrated safety record in people and compatibility with the current CDI therapy, which employs antibiotics targeting gram-positive bacteria, the team chose an E. coli probiotic strain as the host. The probiotic’s sensor picks up sialic acid, a gut chemical that indicates a dysbiosis in the microbiome. When the sialic acid sensor is triggered, the actuator creates an enzyme that can control the metabolism of bile salts. It also inhibits the germination of the Clostridioides difficile spores that cause CDI. The team also added an amplifier to the probiotic, which amplifies sensor activation and enhances enzyme production, reducing Clostridioides difficile spore germination by 98%.
This development that clarifies the gut environment and how it can be changed to produce less invasive treatment methods is encouraging to Assoc Prof Chang. He claims, “This scientific advancement advances our knowledge of how to manipulate the microenvironment within the body without the need of intrusive procedures, additional medications, or direct lethality to eradicate the Clostridioides difficile bacterium. Our focus has moved to investigating how we may develop an antimicrobial strategy to support and supplement the body’s inherent biological processes and help slow the spread of infection. When thinking about the creation or advancement of potential CDI therapies in the future, this is helpful.” READ MORE