Microbial therapy against gut inflammation

Descrizione del progetto

Eludere i meccanismi batterici per ripristinare la composizione del microbiota intestinale

I batteri sono dotati di una capacità intrinseca di regolare l’espressione genica sulla base di fluttuazioni della densità cellulare, un sistema noto come quorum sensing (QS). Nuove prove indicano che il microbiota intestinale impiega diversi percorsi di QS al fine di consentire la comunicazione reciproca tra i suoi microrganismi per il predominio spaziale. Gli scienziati del progetto MAGI, finanziato dall’UE, propongono di sfruttare il QS per affrontare lo squilibrio del microbiota (disbiosi) osservato nella malattia infiammatoria intestinale. L’idea è che la manipolazione del QS allevi l’impatto degli antibiotici e ripristini la composizione del microbiota intestinale, permettendo di recuperarne le funzioni. Dato il ruolo di primaria importanza svolto dal microbiota nello stato metabolico o immunitario dell’ospite, un intervento basato sul QS di tal genere potrebbe offrire ulteriori benefici.

Obiettivo

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.