Gut microbial dysbiosis have been associated with IBD, metabolic disorders and expansion of specific microbiota resident members that can drive inflammation (pathobionts). IBD affects over 5 million people world-wide, with estimate costs to healthcare of 4.6-5.6 thousand million Euros/year. We aim to develop biotherapies that in the long-term can be applied to tackle symptoms (inflammation) and harmful outcomes (hospitalization, surgery, risk of cancer or infections) that would greatly increase patients quality of life, while decreasing time and costs of hospitalizations and medication. Also, the QS-based therapy and the safe-to use engineered biotherapy agent here applied to an IBD mouse model as a proof-of-concept can lead to new prevention and treatment strategies for other microbiota-related diseases associated with gut dysbiosis including infectious diseases, neurological and metabolic disorders, or cancer.
The grant MAGI had the overall objective of taking advantage of microbial interactions mediated by quorum sensing (QS) to tackle gut microbial imbalances (dysbiosis) in inflammatory bowel diseases (IBD).
IBD is characterized by a dysbiotic microbiota and consequent inflammation and loss of protection against pathogenic bacteria. Recovery from dysbiosis into a balanced microbiota can revert these detrimental effects, and QS has been shown to be able to ameliorate dysbiotic microbiota.
In the proposed action we intended to favor beneficial interactions among members of the microbiota in order to promote resilience and re-establishment of normal functions, therefore aiming at an effective therapy to counteract IBD dysbiosis, inflammation, loss of protection against expansion of pathobionts and susceptibility to pathogens. The project was founded on two major pillars:
1. Use an engineered bacterial microbiota strain to manipulate levels of the quorum sensing molecule Auto-inducer 2 (AI-2) in a dysbiotic murine gut;
2. Promote colonization resistance / displacement of IBD-related pathogens or pathobionts and restore balance on an IBD dysbiotic microbiota
We have successfully used a native gut microbiota member as a biotherapy agent against AIEC infection in IBD context, not only capable of displacing the pathobiont, but also of promoting gut microbiota recovery after antibiotic-induced dysbiosis, therefore potentially protecting from subsequent recurrent infections. Hence, we have achieved the proposed main objective of identifying and testing a potential biotherapy to resolve IBD-related symptoms.
