Time‐ and strain‐specific downregulation of intestinal EPAS1 via miR‐148a by Bifidobacterium bifidum. Issue 5 (3rd February 2017)

• Record Type: Journal Article
• Authors: Taibi, Amel; Singh, Natasha; Chen, Jianmin; Arioli, Stefania; Guglielmetti, Simone; Comelli, Elena M.
• Is Part Of: Molecular nutrition & food research. Volume 61:Issue 5(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-02-03
• Subjects: Bifidobacterium bifidum -- EPAS1 -- Intestine -- MicroRNA -- Probiotic -- Time; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201600596
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : We studied if probiotic bifidobacteria alter intestinal microRNA and downstream target gene response. We found that intestinal cells respond to Bifidobacterium bifidum exposure via increased expression of miR‐148a in a time‐dependent manner. At 1 h, an increase in miR‐148a results in decreased expression of its target gene endothelial PAS domain protein 1. EPAS1 is involved in intestinal cancers and inflammation; thus, B. bifidum could provide a strategy to support homeostasis via microRNA. Abstract : Scope: Bifidobacteria play a role in intestinal homeostasis but molecular mechanisms remain underinvestigated. 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 endothelial PAS domain protein 1 ( EPAS1 ) was analyzed in Caco‐2 cells and mice cecum in response to Bifidobacterium bifidum MIMBb75, B. bifidum NCC390, or Bifidobacterium 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 h ( p < 0.01), but not after 24 h. 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 in miR‐148a was accompanied by a decrease in 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.