Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 307, Issue 12, Pages C1084-C1092Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00194.2014
Keywords
antidiarrheal; Caco-2; chloride absorption; downregulated in adenoma
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-54016, DK-81858, DK-92441, DK-71596, DK-096258]
- Bill and Melinda Gates Foundation [OPP1058288]
- Department of Veteran Affairs [BX 002011, BX 000152]
- Bill and Melinda Gates Foundation [OPP1058288] Funding Source: Bill and Melinda Gates Foundation
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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 (similar to 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 mu M) and the ERK1/2 MAPK pathway inhibitor U0126 (10 mu M). 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.
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