Gene expression profiling identifies mechanisms of protection to recurrent trinitrobenzene sulfonic acid colitis mediated by probiotics

Background: Hostmicrobiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain more insight into protective mechanisms. Methods: Moderate chronic inflammation of the colon was induced in BALB/c mice by repetitive intrarectal challenges with TNBS. Administration of probiotics started 2 weeks before colitis induction and was continued throughout colitis development. Results: Long-term administration of Lactobacillus plantarum NCIMB8826 or the probiotic mixture VSL#3 reduced intestinal inflammation induced by TNBS, evident from improved colon morphology and less influx of innate (CD11b+) and adaptive (CD4+/CD8+) immune cells in the intestinal mucosa and decreased proinflammatory serum cytokines (interferon-gamma [IFN-?], interleukin [IL]-17, IL-1 beta, monocyte chemoattractant protein [MCP]-1) in probiotic-treated mice. Genomewide expression analysis of colonic tissues using microarrays revealed differences in expression of genes related to inflammation and immune processes between untreated and probiotic treated mice. Principal component analysis revealed that probiotic treatment resulted in a shift of gene expression profiles toward those of healthy controls. Effects of probiotics on colonic gene expression were most profound during active inflammation, in particular on gene clusters related to mast cells and antimicrobial peptides. The results were substantiated by suppression of chemokine gene expression. Conclusions: Our data are in favor of a model in which probiotics downregulate expression of chemokines in the colon, thereby decreasing influx of inflammatory cells and rendering mice resistant to the induction of colitis. (Inflamm Bowel Dis 2012)