title: Lactobacillus GG-fermented milk prevents DSS-induced colitis and regulates intestinal epithelial homeostasis through activation of epidermal growth factor receptor.
abstract: BACKGROUND
  Fermented milk is considered one of the best sources for efficient consumption of probiotic strains by hosts to promote good health. The purpose of this study was to investigate the effects of orally administering LGG-fermented milk (LGG milk) on intestinal inflammation and injury and to study the mechanisms of LGG milk's action.
  
  
  METHODS
  LGG milk and non-LGG-fermented milk (non-LGG milk) were administered through gavage to mice before and during dextran sodium sulfate (DSS)-induced intestinal injury and colitis. Inflammatory/injury score and colon length were assessed. Intestinal epithelial cells were treated with the soluble fraction of LGG milk to detect its effects on the epidermal growth factor receptor (EGFR) and its downstream target, Akt activation, cytokine-induced apoptosis, and hydrogen peroxide (H2O2)-induced disruption of tight junctions.
  
  
  RESULTS
  LGG milk treatment significantly reduced DSS-induced colonic inflammation and injury, and colon shortening in mice, compared to that in non-LGG milk-treated and -untreated mice. The soluble fraction of LGG milk, but not non-LGG milk, stimulated the activation of EGFR and Akt in a concentration-dependent manner, suppressed cytokine-induced apoptosis, and attenuated H2O2-induced disruption of tight junction complex in the intestinal epithelial cells. These effects of LGG milk were blocked by the EGFR kinase inhibitor. LGG milk, but not non-LGG milk, contained two soluble proteins, p40 and p75, that have been reported to promote survival and growth of intestinal epithelial cells through the activation of EGFR. Depletion of p40 and p75 from LGG milk abolished the effects of LGG milk on prevention of cytokine-induced apoptosis and H2O2-induced disruption of tight junctions.
  
  
  CONCLUSIONS
  These results suggest that LGG milk may regulate intestinal epithelial homeostasis and potentially prevent intestinal inflammatory diseases through activation of EGFR by LGG-derived proteins.
authors.affiliation: Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama, Kanagawa, 241-0023, Japan.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Yoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyazawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Hosoda
authors.forename: Masaru
authors.initials: M
authors.lastname: Hiramatsu
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: Fang
authors.initials: F
authors.lastname: He
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D003611:Dairy Products / Q000382:microbiology*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005285:Fermentation; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D007778:Lactobacillus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D016207:Cytokines; D016264:Dextran Sulfate; D006861:Hydrogen Peroxide; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt