Lactobacillus acidophilus upregulates intestinal NHE3 expression and function

Abstract

A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na(+)/H(+) and Cl(-)/HCO(3)(-) exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl(-)/HCO3- exchange activity via an increase in the surface levels and expression of the Cl(-)/HCO3- exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na(+)/H(+) exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8-24 h resulted in a significant increase in Na(+)/H(+) exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics.

Epithelial Transport in Inflammatory Bowel Diseases

“…Also, enteropathogenic bacteria inhibit (86), whereas commensal Lactobacillus acidophilus upregulates intestinal NHE3 expression and function (87). Inhibition of NHE3 expression and activity has been described in several experimental models of colitis, including IL-2 −/− mice (88), and in DSS- and TNBS-induced colitis (89).…”

Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice

“…This intestinal transport mechanism, mediated primarily by NHE3, plays a critical role in the intestinal sodium and water absorption, regulation of intracellular pH, as well as the acidity of the apical microenvironment. NHE3 expression and/or activity is inhibited by proinflammatory cytokines (3,19) and enteropathogenic bacteria (9), whereas commensal Lactobacillus acidophilus upregulates intestinal NHE3 expression and function (24). Inhibition of NHE3 expression and/or activity has been described in several experimental models of colitis, including IL-2 Ϫ/Ϫ mice (3), IL-10 Ϫ/Ϫ mice (17), and in dextran sodium sulfate (DSS)-and trinitrobenzene sulfonic acid-induced colitis (27).…”

Lactobacillus acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses in Human Intestinal Epithelial Cells

“…Our results demonstrated that Lactobacillus acidophilus , an important gut commensal, counteracted PAF induction of Bcl10-dependent NF-κB activation and IL-8 production in intestinal epithelial NCM460 and Caco-2 cells. Earlier we have shown that this specific strain of L. acidophilus, and more importantly its conditioned culture supernatant, exhibited pro-absorptive effects via distinct mechanisms to stimulate intestinal absorption of NaCl, thereby defining its novel therapeutic potential to ameliorate diarrhea associated with IBD [43], [44]. Interestingly, our current studies also showed that heat-killed LA failed to attenuate PAF-induced increase in nuclear p65 and importantly, bacteria-free CS of LA was as effective as live LA in attenuating the PAF effects on nuclear p65, indicating that LA effects on PAF-induced NF-κB activation are mediated by secreted soluble factor(s) in the CS.…”