Probiotic study: Lactobacillus casei downregulates inflammation in Crohn's

October 13, 2008

Lactobacillus casei downregulates commensals' inflammatory signals in

Crohn's disease mucosa

Marta Llopis, PhD, et al

Abstract

Background: The interaction of commensal bacteria with the intestinal

immune system is an essential factor in the development of

inflammatory bowel disease (IBD). The study of isolated commensal

bacteria's effects on the mucosal immune response might be relevant

for a better understanding of pathophysiological mechanisms in IBD.

Methods: We investigated the immune responses to signals from the

commensal Escherichia coli ATCC 35345 and the probiotic Lactobacillus

casei DN-114 001 in Crohn's disease (CD) mucosa. Ileal specimens were

obtained during surgery from CD patients. Mucosal explants were

incubated with L. casei or its genomic DNA; TNF-, IFN-, IL-2, IL-6,

IL-8, and CXCL1 were measured in the supernatant. Second, tissue

expression of key proinflammatory cytokines (IL-6, TGF-, IL-23p19,

IL-12p35, IL-17F), and chemokines (IL-8, CXCL1, CXCL2) was evaluated

after incubation with L. casei or E. coli. Finally, combination

experiments were carried out by incubating both strains with mucosal

explants at different timepoints.

Results: Live L. casei significantly decreased secretion of TNF-,

IFN-, IL-2, IL-6, IL-8, and CXCL1 by CD mucosa, but the effect was not

reproduced by L. casei DNA. Second, live L. casei downregulated

expression of IL-8, IL-6, and CXCL1 and did not modify expression of

IL-23p19, IL-12p35, and IL-17F. In contrast, E. coli significantly

upregulated expression of all these cytokines. Interestingly,

combination experiments revealed the ability of L. casei to prevent

and counteract the proinflammatory effects of E. coli.

Conclusions: Live L. casei can counteract the proinflammatory effects

of E. coli on CD inflamed mucosa by specific downregulation of key

proinflammatory mediators.

(Inflamm Bowel Dis 2008)

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