W2006 Beneficial Effects of Fermented Milk Containing Lactobacillus GG and L. Gasseri Tmc0356 On Regulating Intestinal Microflora and Immune Responses for Patients with Allergic Disease

Abstract

Background & Aims: TNF DARE/B6 mice develop a chronic and severe intestinal inflammation, primarily localized to the terminal ileum, that is dependent on the global overproduction of TNFα due to a targeted deletion in the 3' untranslated region (UTR) of the TNF gene. The use of probiotics has shown great potential as an effective therapy for the treatment and maintenance of remission in both patients with IBD as well experimental models of colitis. However, the specific mechanism(s) of probiotic efficacy in the treatment of IBD remains to be elucidated. The aim of the present study was to determine whether administration of VSL#3, a probiotic mixture of Streptococcus thermophilus, 3 strains of Bifidobacterium, and 4 strains of lactobacillus, had the ability to decrease the severity of TNF-dependent chronic intestinal inflammation and evaluate potential mechanism(s) for its efficacy. Methods: TNF DARE/B6 and control mice with active and severe ileitis (16 wks of age) were fed a diet supplemented with VSL#3 for a period of 6 wks. In Vivo permeability along the gut axis was evaluated at t=0, 2, 4, and 6 wks and measured by the fractional excretion (FE) of specific sugars in the urine of experimental mice following oral gavage of a sugar probe cocktail administered 18 hrs before collection. Disease activity was assessed by histologic evaluation of ilea after the 6 wk treatment period using an established scoring system, and circulating TNFα protein levels measured by ELISA in the serum of experimental mice. Results: Treatment of TNF DARE/B6 mice with VSL#3 significantly decreased total ileal inflammation compared to untreated control mice (7.75±1.64 vs. 22.8±1.88, p<0.001). Administration of VSL#3 also resulted in a dramatic and significant decrease of serum TNFα protein levels in treated versus untreated TNF DARE/B6 mice (25.86±7.95 vs. 184.68±58.14 pg/ml, p=0.01). Finally, small intestinal permeability was significantly lower in VSL#3treated TNF DARE/B6 mice compared to mice with established ileitis (0.358±0.0096 vs. 0.779±0.031 lactulose/mannitol FE, p<0.001). Conclusion: Our results demonstrate that administration of the probiotic mixture, VSL#3, had the ability to ameliorate the severity of TNF-dependent experimental ileitis by potentially decreasing circulating TNF levels and improving overall epithelial barrier function in the gut. These data underscore the critical role in regulating TNFα expression for the treatment of chronic intestinal inflammation, such as that observed in IBD.