C. difficile infection, an infection that causes infectious diarrhea, is difficult to treat and can be fatal, is mostly seen in people who have taken antibiotics and have just finished treatment. Indeed, antibiotics lead to an imbalance of the intestinal microbiome or dysbiosis, which disrupts other microbiome processes such as bile salt metabolism and eliminates “good bacteria”. Dysregulation of bile salt metabolism also reactivates dormant spores of Clostridioides difficilewhich induces irritable bowel syndrome with symptoms of severe diarrhea and colitis.
A smart probiotic that fights dysbiosis
The Singapore team, led by Professor Matthew Chang, a biologist at NUS Medicine, has designed a probiotic capable of detecting the appearance of an imbalance in the microbiome induced by antibiotics and which expresses an enzyme making it possible to regulate the metabolism of bile salts.
This probiotic contains a genetic circuit that includes a genetically coded sensor, amplifier and switch.
Initially, a probiotic strain of E. coli as a host due to its proven safety profile in humans and its gram-negative nature which makes it compatible with current therapy for irritable bowel syndrome, which uses antibiotics targeting gram-positive bacteria:
- the sensor of this probiotic detects the presence of sialic acid, an intestinal metabolite that indicates an imbalance in the microbiome;
- a switch triggers the production of an enzyme that regulates bile salt metabolism and reduces the germination of C. difficile spores that induce colon inflammation;
- an enhancer still “in the probiotic”, amplifies sensor activation and increases enzyme production, further reducing C. difficile spore reactivation by up to 98%.
Preclinical evidence: experiments on animal models confirm that the probiotic significantly reduces irritable bowel syndrome, leads to better clinical results and ensures a 100% survival rate.
Regulate the intestinal environment Where the microbiota to create less invasive treatment strategies, and in this case without the need to kill certain bacterial strains live (here C. difficile), to give drugs or to use invasive methods, is certainly a promising way to fight against intestinal diseases and infections, but not only.
Here, the concept is to inspire, complement and reinforce natural biological processes in the body in order to limit the development of infection.