title: Time- and strain-specific downregulation of intestinal EPAS1 via miR-148a by Bifidobacterium bifidum.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Nutritional Sciences, University of Toronto, ON, Canada.
authors.forename: Amel
authors.initials: A
authors.lastname: Taibi
authors.affiliation: Department of Nutritional Sciences, University of Toronto, ON, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Nutritional Sciences, University of Toronto, ON, Canada.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nutritional Sciences, University of Toronto, ON, Canada.|Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Arioli
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Guglielmetti
authors.affiliation: Department of Nutritional Sciences, University of Toronto, ON, Canada.|Centre for Child Nutrition and Health, Faculty of Medicine, University of Toronto, ON, Canada.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Comelli
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D000069985:Bifidobacterium bifidum; D018938:Caco-2 Cells; D002432:Cecum / Q000378:metabolism / Q000382:microbiology; D015536:Down-Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019936:Probiotics / Q000008:administration & dosage*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; D000099162:Endothelial PAS Domain-Containing Protein 1; C550570:MIRN148 microRNA, human; C554644:Mirn148 microRNA, mouse
keywords: Bifidobacterium bifidum; EPAS1; Intestine; MicroRNA; Probiotic; Time