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Microbial therapy against gut inflammation

Microbial therapy against gut inflammation

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.
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Coordinator

FUNDACAO CALOUSTE GULBENKIAN

Address

Avenida Berna 45
1000 Lisboa

Portugal

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 147 815,04

Project information

Grant agreement ID: 843183

Status

Grant agreement signed

  • Start date

    1 October 2019

  • End date

    30 September 2021

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 147 815,04

  • EU contribution

    € 147 815,04

Coordinated by:

FUNDACAO CALOUSTE GULBENKIAN

Portugal