Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC).
BACKGROUND
The colonic epithelium maintains a life long reciprocally beneficial interaction with the colonic microbiota. Disruption is associated with mucosal injury.


OBJECTIVE
We hypothesised that probiotics may limit epithelial damage induced by enteroinvasive pathogens, and promote restitution.


METHODS
Human intestinal epithelial cell lines (HT29/cl.19A and Caco-2) were exposed to enteroinvasive Escherichia coli (EIEC 029:NM), and/or probiotics (Streptococcus thermophilus (ST), ATCC19258, and Lactobacillus acidophilus (LA), ATCC4356). Infected cells and controls were assessed for transepithelial resistance, chloride secretory responses, alterations in cytoskeletal and tight junctional proteins, and responses to epidermal growth factor (EGF) stimulation.


RESULTS
Exposure of cell monolayers to live ST/LA, but not to heat inactivated ST/LA, significantly limited adhesion, invasion, and physiological dysfunction induced by EIEC. Antibiotic killed ST/LA reduced adhesion somewhat but were less effective in limiting the consequences of EIEC invasion of cell monolayers. Furthermore, live ST/LA alone increased transepithelial resistance, contrasting markedly with the fall in resistance evoked by EIEC infection, which could also be blocked by live ST/LA. The effect of ST/LA on resistance was accompanied by maintenance (actin, ZO-1) or enhancement (actinin, occludin) of cytoskeletal and tight junctional protein phosphorylation. ST/LA had no effect on chloride secretion by themselves but reversed the increase in basal secretion evoked by EIEC. EIEC also reduced the ability of EGF to activate its receptor, which was reversed by ST/LA.


CONCLUSIONS
Live ST/LA interact with intestinal epithelial cells to protect them from the deleterious effect of EIEC via mechanisms that include, but are not limited to, interference with pathogen adhesion and invasion. Probiotics likely also enhance the barrier function of naïve epithelial cells not exposed to any pathogen.
Resta-Lenert
S
S
Department of Medicine, School of Medicine, University of California-San Diego, UCSD Medical Center 8414, 200 West Arbor Drive, San Diego, CA 92103, USA. srestalenert@ucsd.edu
Barrett
K E
KE
D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D003108:Colonic Diseases / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D015169:Colony Count, Microbial; D003599:Cytoskeleton / Q000378:metabolism; D003967:Diarrhea / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D066246:ErbB Receptors / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D007779:Lactobacillus acidophilus; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D019936:Probiotics / Q000627:therapeutic use*; D013291:Streptococcus
D002712:Chlorides; D008565:Membrane Proteins; D066246:ErbB Receptors