P039 - FECAL miRNAs SHAPE THE INTESTINAL MICROBIOTA
(Room Poster Hall)
19 Jan 18
5:30 PM
-
7:00 PM
Tracks:
Clinical and Research Challenges
Inflammatory Bowel Diseases are associated with a disruption of the intestinal microbiota, called dysbiosis, determining event in the pathogenesis. Interactions between host and microbiota occur through various factors, including anti-microbial peptides. Recently, we and others have identified fecal miRNAs as new functional entities in the gut that could play a role on both microbiota and intestinal homeostasis. We hypothesize here that fecal miRNAs are a third player in the microbiota-host interaction that can mediate direct microbiota alterations that will in turn impact the host. Fecal miRNA profiling was performed in IL10-/- mice with (115 day-old) or without (37 day-old) colitis. In order to investigate the functional role played by fecal miRNAs, colitis-associated miRNAs or scramble RNAs were orally administered to WT recipient mice. Microbiota composition, diversity, localization and pro-inflammatory potential were analyzed. We identified that fecal miRNA profile is altered in colitic IL10-/- mice compared to pre-colitic IL10-/- mice. Particularly, 2 miRNAs were up-regulated (let-7b-5p and miR-21a-5p) and 6 were down-regulated. Interestingly, we found that mice orally treated with a combination of let-7b-5p and miR-21a-5p had a rapid change in their microbiota composition, characterized by a decrease in diversity and in the abundance of Akkermansia muciniphila, a mucin-degrading bacterium known to be inversely correlated with inflammation. Fecal LPS and FLiC were significantly increased after miRNAs administration, indicating that the microbiota of mice treated with colitis-associated miRNAs was more pro-inflammatory. Our data demonstrate that functional fecal miRNAs are modulated by intestinal inflammation and can alter the microbiota. That miRNAs actively regulate the microbiota provides a unique opportunity to manipulate this complex community in a way that can benefit the host and ultimately patients with dysbiosis-associated inflammation.