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.