Lactobacillus acidophilus.pdf (1.38 MB)
Download fileLactobacillus acidophilus counteracts inhibition of NHE3 and DRA expression and alleviates diarrheal phenotype in mice infected with Citrobacter rodentium
journal contribution
posted on 2017-05-18, 00:00 authored by Pradeep K. Dudeja, Alip Borthakur, Waddah A. Alrefai, Ravinder K. Gill, Seema Saksena, Tarunmeet Gujral, Shubha Priyamvada, Ishita Chatterjee, Hayley Coffing, Arivarasu Natarajan Anbazhagan, Anoop KumarImpaired 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-1 , IFN- , and CXCL1 mRNA and C. rodentiuminduced
STAT3 phosphorylation. In conclusion, our data provide
mechanistic insights into antidiarrheal effects of LA in a model of
infectious diarrhea and colitis.