Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance

Abstract

Background: Prophylactic efficacy against colitis following lactobacillus consumption in interleukin 10 (IL-10) knockout (KO) mice has been reported. Whether this applies equally to other probiotic strains is unknown, and the mechanism is unclear. Aims: (1) To compare the effect of feeding Lactobacillus salivarius subspecies salivarius 433118 and Bifidobacterium infantis 35624 against placebo on enterocolitis, the intestinal microflora, and (2) to compare the systemic immunological response to in vitro microbial challenge in probiotic fed and control IL-10 KO mice. Methods: Three groups of 10 IL-10 KO mice were fed fermented milk products containing Lb salivarius 433118 at 10 9 CFU/ml, B infantis 35624 at 10 8 CFU/ml, and unmodified milk, respectively, for 19 weeks. Faecal samples were taken at regular intervals to confirm gut transit, recovery of fed probiotics, and to assess the impact on the microflora. At sacrifice, the bowels were histologically scored. Cytokine production from Peyers' patches and splenocytes was measured in vitro by ELISA. Results: Faecal recovery of probiotics was confirmed in all probiotic fed mice but not in controls. Colonic and caecal inflammatory scores were significantly decreased in both groups of probiotic fed mice (p<0.05). Proinflammatory cytokine production by Peyers' patches and splenocytes was significantly reduced in probiotic fed animals whereas transforming growth factor β (TGF-β) levels were maintained. Conclusion: Both Lactobacillus salivarius 433118 and Bifidobacterium infantis 35624 significantly attenuate colitis in this murine model. Attenuation of colitis is associated with a reduced ability to produce Th1-type cytokines systemically and mucosally, while levels of TGF-β are maintained.

Innate mechanisms for Bifidobacterium lactis to activate transient pro‐inflammatory host responses in intestinal epithelial cells after the colonization of germ‐free rats

“…B. lactis HN019 also revealed immune stimulatory functions in elderly people including effects on natural killer cell and granulocyte activation. 39 In addition, B. infantis strain 35624 attenuated experimental chronic colitis in IL-10 -/-mice 40 and dextran sodium sulphate-induced acute colitis in Sprague-Dawley rats. 41 Furthermore, the probiotic mixture VSL#3 with eight different lactic acid bacterial species including B. longum, B. infantis and B. breve were effective in the treatment and/or treatment of experimental colitis in IL-10 -/-mice 42 as well as inflammatory bowel disease patients with pouchitis.…”

Probiotics and immunity

“…salivarius 433118 and B. infantis 35624, 103 the therapeutic effect of DNA isolated from VSL#3, 48 and the partial protection provided by preventative and therapeutic administration of L. plantarum 299v in IL-10 −/− mice. 104 Interestingly, in SCID mice reconstituted with activated CD4+ T cells or CD4+CD62L+ T cells, preventative treatment with a combination of L. reuteri DSM 12246 and L. rhamnosus 19070-2 or with E. coli Nissle was associated with signifi cantly decreased production of Th2 cytokines by polyclonally stimulated MLNs.…”

Diversity of the genus Lactobacillus revealed by comparative genomics of five species

“…This strain was isolated from the terminal ileum of a healthy human subject undergoing reconstructive urinary tract surgery (Dunne et al, 1999). It has been extensively studied for its probiotic properties in human trials and animal models (Dunne et al, 1999(Dunne et al, , 2001McCarthy et al, 2003;Sheil et al, 2004). Members of this species are commonly isolated from the oral and GI tracts of humans and other animals (Ahrne et al, 1998;Heilig et al, 2002;Molin et al, 1993;Rogosa et al, 1953).…”