The team used an E. coli probiotic strain as the host because of its proven safety record in humans and its gram-negative nature makes it compatible with the current CDI therapy that uses antibiotics targeting gram-positive bacteria. The sensor in this probiotic, detects the presence of sialic acid, a gut metabolite that is indicative of microbiome imbalance. The actuator produces an enzyme that can regulate the bile salt metabolism, activated by the sensor, and it reduces the germination of the Clostridioides difficile spores that causes CDI, when induced by the sialic acid sensor. The team also included an amplifier in the probiotic which amplifies the activation by the sensor and increases the production of the enzyme, reducing the germination of the Clostridioides difficile spores by 98%. Experiments showed that the probiotic significantly reduced CDI in laboratory models, as demonstrated by a 100% survival rate and improved clinical outcomes.
Assoc Prof Chang is encouraged by this advancement that sheds more light on the gut environment and how it can be manipulated to create less invasive treatment strategies. He says, “This scientific innovation gives a better understanding on how we can control the microenvironment in the body, without needing to exert direct lethality to kill the Clostridioides difficile bacterium, give additional drugs, or use invasive methods to rid the infection. Our perspectives have shifted towards studying how we can come up an antimicrobial strategy to complement and assist the natural biological processes in the body to help limit the onset of infection. This is useful when considering the development or improvement of future therapeutics for CDI.”
The paper was published in Nature Communications in July 2022.
More information: Elvin Koh et al, Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism, Nature Communications (2022). DOI: 10.1038/s41467-022-31334-z
Citation: Scientists engineer probiotic to prevent infection of large intestine (2022, August 4) retrieved 4 August 2022 from https://medicalxpress.com/news/2022-08-scientists-probiotic-infection-large-intestine.html
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