title: Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells.
abstract: SLC26A3, or downregulated in adenoma (DRA), plays a major role in mediating Cl(-) absorption in the mammalian intestine. Disturbances in DRA function and expression have been implicated in intestinal disorders such as congenital Cl(-) diarrhea and gut inflammation. We previously showed that an increase in DRA function and expression by Lactobacillus acidophilus and its culture supernatant (CS) might underlie antidiarrheal effects of this probiotic strain. However, the effects of Bifidobacterium species, important inhabitants of the human colon, on intestinal Cl(-)/HCO3 (-) exchange activity are not known. Our current results demonstrate that CS derived from Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium bifidum increased anion exchange activity in Caco-2 cells (∼1.8- to 2.4-fold). Consistent with the increase in DRA function, CS also increased the protein, as well as the mRNA, level of DRA (but not putative anion transporter 1). CS of all three Bifidobacterium sp. increased DRA promoter activity (-1,183/+114 bp) in Caco-2 cells (1.5- to 1.8-fold). Furthermore, the increase in DRA mRNA expression by CS of B. breve and B. infantis was blocked in the presence of the transcription inhibitor actinomycin D (5 μM) and the ERK1/2 MAPK pathway inhibitor U0126 (10 μM). Administration of live B. breve, B. infantis, and B. bifidum by oral gavage to mice for 24 h increased DRA mRNA and protein levels in the colon. These data demonstrate an upregulation of DRA via activation of the ERK1/2 pathway that may underlie potential antidiarrheal effects of Bifidobacterium sp.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; Singhania University Pacheri Bari, Rajasthan, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Cameron
authors.initials: C
authors.lastname: Hecht
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Shubha
authors.initials: S
authors.lastname: Priyamvada
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Arivarasu N
authors.initials: AN
authors.lastname: Anbazhagan
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Anas
authors.initials: A
authors.lastname: Alakkam
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Alip
authors.initials: A
authors.lastname: Borthakur
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; and.
authors.forename: Waddah A
authors.initials: WA
authors.lastname: Alrefai
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Ravinder K
authors.initials: RK
authors.lastname: Gill
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; and pkdudeja@uic.edu.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dudeja
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D001644:Bifidobacterium / Q000145:classification / Q000502:physiology*; D018938:Caco-2 Cells; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019936:Probiotics; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D000076988:Sulfate Transporters; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
chemical_list: D017920:Antiporters; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D019384:Nucleic Acid Synthesis Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C081011:SLC26A3 protein, human; C489860:Slc26a3 protein, mouse; D000076988:Sulfate Transporters; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Caco-2; antidiarrheal; chloride absorption; downregulated in adenoma