title: The probiotic Lactobacillus plantarum counteracts TNF-{alpha}-induced downregulation of SMCT1 expression and function.
abstract: The major short-chain fatty acid (SCFA) butyrate is produced in the colonic lumen by bacterial fermentation of dietary fiber. Butyrate serves as primary fuel for the colonocytes and also ameliorates mucosal inflammation. Disturbed energy homeostasis seen in inflamed mucosa of inflammatory bowel disease patients has been attributed to impaired absorption of butyrate. Since sodium-coupled monocarboxylate transporter 1 (SMCT1, SLC5A8) has recently been shown to play a role in Na(+)-coupled transport of monocarboxylates, including SCFA, such as luminal butyrate, we examined the effects of proinflammatory TNF-α on SMCT1 expression and function and potential anti-inflammatory role of probiotic Lactobacillus species in counteracting the TNF-α effects. Rat intestinal epithelial cell (IEC)-6 or human intestinal Caco-2 cells were treated with TNF-α in the presence or absence of Lactobacilli culture supernatants (CS). TNF-α treatments for 24 h dose-dependently inhibited SMCT1-mediated, Na(+)-dependent butyrate uptake and SMCT1 mRNA expression in IEC-6 cells and SMCT1 promoter activity in Caco-2 cells. CS of L. plantarum (LP) stimulated Na(+)-dependent butyrate uptake (2.5-fold, P < 0.05), SMCT1 mRNA expression, and promoter activity. Furthermore, preincubating the cells with LP-CS followed by coincubation with TNF-α significantly attenuated the inhibitory effects of TNF-α on SMCT1 function, expression, and promoter activity. In vivo, oral administration of live LP enhanced SMCT1 mRNA expression in the colonic and ileal tissues of C57BL/6 mice after 24 h. Efficacy of LP or their secreted soluble factors to stimulate SMCT1 expression and function and to counteract the inhibitory effects of TNF-α on butyrate absorption could have potential therapeutic value.
authors.affiliation: Dept. of Medicine, Univ. of Illinois at Chicago, Jesse Brown Veterans Affairs Medical Center, 60612, USA. alipb@uic.edu
authors.forename: Alip
authors.initials: A
authors.lastname: Borthakur
authors.forename: Arivarasu N
authors.initials: AN
authors.lastname: Anbazhagan
authors.forename: Anoop
authors.initials: A
authors.lastname: Kumar
authors.forename: Geetu
authors.initials: G
authors.lastname: Raheja
authors.forename: Varsha
authors.initials: V
authors.lastname: Singh
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Ramaswamy
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dudeja
mesh_terms: D000818:Animals; D002087:Butyrates / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D048191:Lactiplantibacillus plantarum / Q000502:physiology*; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002087:Butyrates; D027682:Cation Transport Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C476760:SLC5A8 protein, human; C553109:SLC5A8 protein, rat; C507459:Slc5a8 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D012964:Sodium