Abstract

Impaired absorption of electrolytes is a hallmark of diarrhea associated with inflammation or enteric infections. Intestinal epithelial luminal membrane NHE3 (Na+/H+ exchanger 3) and DRA (Down-Regulated in Adenoma; Cl-/HCO3- exchanger) play key roles in mediating electroneutral NaCl absorption. We have previously shown decreased NHE3 and DRA function in response to short-term infection with enteropathogenic E coli (EPEC), a diarrheal pathogen. Recent studies have also shown substantial downregulation of DRA expression in a diarrheal model of infection with Citrobacter rodentium, the mouse counterpart of EPEC. Since our previous studies showed that the probiotic Lactobacillus acidophilus (LA) increased DRA and NHE3 function and expression and conferred protective effects in experimental colitis, we sought to evaluate the efficacy of LA in counteracting NHE3 and DRA inhibition and ameliorating diarrhea in a model of C rodentium infection. FVB/N mice challenged with C rodentium [1 × 109 colony-forming units (CFU)] with or without administration of live LA (3 × 109 CFU) were assessed for NHE3 and DRA mRNA and protein expression, mRNA levels of carbonic anhydrase, diarrheal phenotype (assessed by colonic weight-to-length ratio), myeloperoxidase activity, and proinflammatory cytokines. LA counteracted C rodentium-induced inhibition of colonic DRA, NHE3, and carbonic anhydrase I and IV expression and attenuated diarrheal phenotype and MPO activity. Furthermore, LA completely blocked C rodentium induction of IL-1β, IFN-γ, and CXCL1 mRNA and C rodentium-induced STAT3 phosphorylation. In conclusion, our data provide mechanistic insights into antidiarrheal effects of LA in a model of infectious diarrhea and colitis.

Highlights

  • Dysregulated ion transport is a hallmark of diarrhea

  • Our previous studies demonstrated the efficacy of the probiotic Lactobacillus acidophilus (LA) in enhancing Naϩ/Hϩ exchanger isoform 3 (NHE3) and DRA expression and function and in counteracting inflammation-induced downregulation of DRA expression and function in both in vitro and in vivo models [4, 27, 34, 35]

  • Citrobacter rodentium (CR)-induced downregulation of NHE3 mRNA and the counteracting effects of LA were more pronounced in the distal colon compared with proximal colon, presumably due to greater colonization of the pathogen in distal colon [14]

Read more

Summary

Introduction

Present studies examined the alleviation of downregulation of the expression of NHE3 and DRA by the probiotic Lactobacillus acidophilus in a murine model of infection by Citrobacter rodentium, a diarrheal pathogen. THE MODEL OF INFECTION WITH the murine pathogen Citrobacter rodentium (CR) has been used to complement in vitro studies of enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) infections of human intestinal epithelial cells (IECs) [11]. Impairment of normal intestinal ion transport processes is a hallmark of infectious diarrhea [3, 21] as well as diarrhea associated with IBD [26] In this regard, our previous studies indicated that decreased absorption rather than an increased secretion could be primarily responsible for early onset of EPEC-induced diarrhea (18 –20). EPEC infection decreased activities of both NHE3 and DRA, the key intestinal epithelial http://www.ajpgi.org

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call