H2020Индивидуална стипендия2019–2021

MAGI · Microbial therapy against gut inflammation

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-10-01 → 2021-09-30
Финансиране от ЕС: 147 815 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Микробните взаимодействия чрез т.нар. „quorum sensing“ се изследват, за да се възстанови балансът на бактериите при възпалителни заболявания на червата. Това може да подобри качеството на живот на пациентите и да намали нуждата от хоспитализации и операции.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Microbial therapy against gut inflammation

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACAO CALOUSTE GULBENKIAN · LisboaКоординаторПортугалия