Time and strain-specific downregulation of intestinal EPAS1 via miR-148a by Bifidobacterium bifidum

cope Bifidobacteria play a role in intestinal homeostasis but molecular mechanisms remain under-investigated. The aim of this study was to assess if probiotic Bifidobacterium strains alter expression of intestinal microRNA and downstream target gene response. Methods and results The expression of miR-148a and its validated target EPAS1 (endothelial PAS domain protein 1) was analyzed in Caco-2 cells and mice cecum in response to Bifidobacterium bifidum MIMBb75, B. bifidum NCC390 or B. longum NCC2705. In vitro, exposure to B. bifidum MIMBb75, but not to B. bifidum NCC390 or B. longum NCC2705, increased the expression of miR-148a after 1 and 4 hours (P <0.01), but not after 24h. In vivo, B. bifidum MIMBb75 administration to C57BL/6J mice increased miR-148a expression in the cecum after 2 but not 14 days (P< 0.05). The increase of miR-148a was accompanied by a decrease of EPAS1 expression in Caco-2 cells and cecum (P<0.05). Silencing of miR-148a reversed B. bifidum MIMBb75-dependent downregulation of EPAS1. Conclusion This study shows an early response of intestinal cells to B. bifidum MIMBb75 through miR-148a modulation. This brings a new concept of strain- and time-dependent bifidobacteria-host crosstalk via microRNA. Probiotic B. bifidum MIMBb75 may help attenuating EPAS1 overexpression associated with intestinal inflammation. This article is protected by copyright. All rights reserved