Project description
Hijacking bacterial mechanisms to restore gut microbiota composition
Bacteria have an inherent capacity to regulate gene expression based on fluctuations in cell density, an attribute known as quorum sensing (QS). Emerging evidence indicates that gut microbiota employ different pathways of QS to communicate with each other for spatial dominance. Scientists of the EU-funded MAGI project propose to exploit QS to address the imbalanced microbiota (dysbiosis) observed in inflammatory bowel disease. The idea is that manipulation of QS will alleviate the impact of antibiotics and restore gut microbiota composition and hence function. Given the central role of microbiota in the metabolic or immune status of the host, a QS-based intervention may have additional benefits.
Objective
Gut microbiota support intestinal tract development, immune system maturation, and protection against pathogens. Imbalanced microbiota (dysbiosis) has a role in inflammatory bowel disease (IBD). To control inflammation, patients take antibiotics, exacerbating dysbiosis, leading to loss of colonization resistance against pathogens and proliferation of pathobionts, disease development and progression. Microbiota composition has, therefore, a very important role in host health, and strategies to manipulate this composition are lacking. Microbiota-produced molecules, like quorum sensing (QS) signal autoinducer-2, can influence gut composition. Bacteria use QS to regulate populational gene expression. We intend to take advantage of microbial interactions mediated by QS to tackle IBD dysbiosis. We will design biotherapies to attenuate the detrimental dysbiotic effects on host health, focusing on gut QS in IBD. The microbiota imbalance observed in IBD leads to high inflammation, expansion of pathobionts, and loss of protection against infections. In previous work, we have shown that by committing the gut microbiota to inter-species QS we could increase members of the microbiota affected by antibiotics, highlighting the potential of QS manipulation to counteract dysbiosis. We propose to manipulate QS of native gut microbes to counteract IBD-associated dysbiosis, and thus inflammation and loss of protection associated with it, rescuing normal microbiota functions. We will tackle dysbiosis by manipulating QS signalling and by fostering specific beneficial interactions amongst microbes. The potential of this therapy, as an alternative or complement to antibiotics, is centred on bypassing the worsening of dysbiosis, like loss of protection against the expansion of inflammation-driving pathobionts and infections, as well as the attenuation of inflammation.
Fields of science
Not validated
Not validated
Programme(s)
Funding Scheme
MSCA-IF-EF-RI - RI – Reintegration panelCoordinator
1067-001 Lisboa
Portugal