Lactobacillus acidophilus counteracts enteropathogenic E. coli-induced inhibition of butyrate uptake in intestinal epithelial cells.
Butyrate, a key short-chain fatty acid metabolite of colonic luminal bacterial action on dietary fiber, serves as a primary fuel for the colonocytes, ameliorates mucosal inflammation, and stimulates NaCl absorption. Absorption of butyrate into the colonocytes is essential for these intracellular effects. Monocarboxylate transporter 1 (MCT1) plays a major role in colonic luminal butyrate absorption. Previous studies (Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. Adv Immunol 121: 91-119, 2014.) showed decreased MCT1 expression and function in intestinal inflammation. We have previously shown (Borthakur A, Gill RK, Hodges K, Ramaswamy K, Hecht G, Dudeja PK. Am J Physiol Gastrointest Liver Physiol 290: G30-G35, 2006.) impaired butyrate absorption in human intestinal epithelial Caco-2 cells due to decreased MCT1 level at the apical cell surface following enteropathogenic E. coli (EPEC) infection. Current studies, therefore, examined the potential role of probiotic Lactobacilli in stimulating MCT1-mediated butyrate uptake and counteracting EPEC inhibition of MCT1 function. Of the five species of Lactobacilli, short-term (3 h) treatment with L. acidophilus (LA) significantly increased MCT1-mediated butyrate uptake in Caco-2 cells. Heat-killed LA was ineffective, whereas the conditioned culture supernatant of LA (LA-CS) was equally effective in stimulating MCT1 function, indicating that the effects are mediated by LA-secreted soluble factor(s). Furthermore, LA-CS increased apical membrane levels of MCT1 protein via decreasing its basal endocytosis, suggesting that LA-CS stimulation of butyrate uptake could be secondary to increased levels of MCT1 on the apical cell surface. LA-CS also attenuated EPEC inhibition of butyrate uptake and EPEC-mediated endocytosis of MCT1. Our studies highlight distinct role of specific LA-secreted molecules in modulating colonic butyrate absorption.
Department of Medicine, Division of Gastroenterology & Hepatology, University of Illinois at Chicago, Chicago, Illinois; and.
Anoop
A
Kumar
Department of Medicine, Division of Gastroenterology & Hepatology, University of Illinois at Chicago, Chicago, Illinois; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Waddah A
WA
Alrefai
Department of Medicine, Division of Gastroenterology & Hepatology, University of Illinois at Chicago, Chicago, Illinois; and alipb@uic.edu.
Alip
http://orcid.org/0000-0002-5792-1279
A
Borthakur
Department of Medicine, Division of Gastroenterology & Hepatology, University of Illinois at Chicago, Chicago, Illinois; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Pradeep K
PK
Dudeja
D001692:Biological Transport; D019921:Biotinylation; D020148:Butyric Acid / Q000378:metabolism*; D018938:Caco-2 Cells; D018929:Cell Culture Techniques; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D007422:Intestines / Q000382:microbiology; D007779:Lactobacillus acidophilus / Q000502:physiology*
D020148:Butyric Acid
Caco-2; SCFA; endocytosis; pCMBS; probiotics