A synbiotic upregulates MCT1 expression and butyrate transport in intestinal epithelial cells

Butyrate, an energy substrate and gene regulator, is transported across the apical aspect of intestinal epithelial cells (IEC) by the monocarboxylate transporter 1 (MCT1). MCT1 expression is also modulated by butyrate as well as other short chain fatty acids (SCFA), byproducts of bacterial metabolism. We have shown that probiotics ( S.thermophilus , ST, and L.acidophilus , LA) promote intestinal homeostasis by activating a complex gene expression program. We hypothesized that treatment of IEC with ST/LA with or without inulin, a prebiotic, may modulate expression of MCT1 and butyrate transport in IEC. Caco‐2 and HT29/cl.19A cells were grown as monolayers and treated for 24–48 h with butyrate (Buty, 1–10 mM), ST/LA alone or with inulin (0.1–1%, ST/LA/IN), or with commensal bacteria ( B.thethaiotaomicron , BT) with or without IN. Buty upregulated both MCT1 mRNA and protein as expected. Only ST/LA/IN, but not ST/LA, BT nor BT/IN, increased MCT1 expression (>2‐fold vs. Buty, p<0.01) in IEC. Induction of the MCT1 protein by both Buty and ST/LA/IN resulted in a significant increase in [U− 14 C]butyrate transport (3‐fold (p<0.01) and 5‐fold (p<0.001), respectively, vs. controls). Treatment of IEC with ERK or p38 MAP kinase inhibitors (PD98059 and SB203580, respectively) blocked the effects of ST/LA/IN, while only inhibition of p38 significantly reversed effects of Buty in IEC. These data confirm that colonic homeostasis reflects complex interactions of the microbiota and its byproducts with IEC and suggest a role for synbiotics in conditions associated with decreased SCFAs, including inflammatory bowel disease and colon cancer. Supported by NIH grant DK062096 to SRL.