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CORDIS

Fecal miRNAs, new mediators of host-microbiota interaction in Inflammatory Bowel Disease

Project description

Small RNA molecules in our poo may mediate changes leading to chronic bowel inflammation

Our intestine is host to millions of microorganisms that make up our intestinal microbiota and play a critical role in health and disease. Changes in microbiota composition with inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease may be related to changes in intestinal microRNAs (miRNAs). miRNAs are a recently discovered family of small non-coding RNA molecules that modulate gene expression post-transcriptionally and are implicated in a variety of clinical diseases. miR-IBD is investigating whether changes in faecal miRNAs modulate intestinal microbiota, mediating chronic intestinal inflammation in IBD. Aside from highlighting potential diagnostic and therapeutic pathways for IBD, miRNA modulation of host-microbiota interactions could be relevant to similar processes such as parasite-host and parasite-microbiota interactions.

Objective

Growing evidences indicate that microRNAs (miRNAs) are present in various body fluids and contribute to cell-cell communication. My previous studies identified circulating miRNAs as efficient tool for the diagnosis and surveillance of Inflammatory Bowel Disease (IBD). Interestingly, miRNAs are secreted into the intestinal lumen where thousands of different bacterial species are present and confer important benefits to the host. This proximity prompted us to speculate that miRNAs and bacteria interact, playing a role in the host/microbiota relationship. My preliminary data generated to date demonstrate that fecal miRNAs are altered during intestinal inflammation in association with an alteration of microbiota composition, and we recently reported that exogenously administered miRNAs have the potential to alter microbiota composition and function. Here, our central hypothesis is that fecal miRNAs are mediators of host-microbiota interactions and therefore modulate intestinal inflammation. On the basis of this overarching hypothesis, I now propose to determine the role played by the intestinal microbiota in miRNA-mediated modulation of intestinal inflammation (objective 1: mechanism); Investigate the ability of specific miRNAs / anti-miRNAs to modulate intestinal inflammation. (objective 2: therapeutic) and to identify whether fecal miRNAs are indicators of microbiota and intestinal healthiness in IBD patients (objective 3: translational). We envision that the proposed experiments could identify a new role for miRNAs in manipulating the intestinal microbiota hence leading to the development of new therapeutic strategies.

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 196 707,84
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 196 707,84