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.