The Probiotic Mixture VSL#3 Has Differential Effects on Intestinal Immune Parameters in Healthy Female BALB/c and C57BL/6 Mice.

ABSTRACT

BACKGROUND: Probiotic bacteria may render mice resistant to the development of various inflammatory and infectious diseases. OBJECTIVE: This study aimed to identify mechanisms by which probiotic bacteria may influence intestinal immune homeostasis in noninflammatory conditions. METHODS: The effect of VSL#3, a mixture of 8 probiotic bacteria, on intestinal gene expression was studied in healthy female BALB/c and C57BL/6 mice after prolonged oral treatment (28 d, triweekly) with 3 × 10(8) colony-forming units of VSL#3. In a separate experiment in BALB/c mice, the effects of prolonged administration of VSL#3 and of phosphate-buffered saline (PBS), followed by 1 single dose of VSL#3, on innate and adaptive immune cells were evaluated. RESULTS: Microarray analysis of the intestines of mice treated with PBS confirmed well-established differences in the expression of immune-related genes between C57BL/6 and BALB/c mice. Prolonged administration of VSL#3 was associated with downregulation of Il13 [fold change (FC) = 0.46] and Eosinophil peroxidase (Epx) (FC = 0.44) and upregulation of Il12rb1 (FC = 2.1), C-C chemokine receptor type 5 (Ccr5) (FC = 2.6), chemokine (C-X-C motif) receptor 3 (Cxcr3) (FC = 1.6), and C-X-C motif chemokine 10 (Cxcl10) (FC = 2.8) in BALB/c mice but not in C57BL/6 mice. In BALB/c mice, it was shown that 28 d of treatment with VSL#3 affected the Peyer's patches (PPs) and mesenteric lymph nodes (MLNs), which was evident from an increase in B cells (26% and 8%, respectively), a decrease in T cells (21% and 8%, respectively), and an increase in cluster of differentiation (CD) 11c(+) cells (57% in PPs) compared with PBS-treated mice. This treatment was also associated with increased frequencies of T helper 17 (13%) and regulatory T cells (11%) in the MLNs. Treatment with PBS followed by 1 single dose of VSL#3, 18 h before killing, was associated with a 2-fold increase in CD103(+)CD11c(+) dendritic cells in MLNs and PPs. CONCLUSION: VSL#3 treatment mediates mouse strain-specific alterations in immunologic phenotype in conditions of homeostasis, suggesting that the effects of probiotic bacteria depend on the genetic background of the host.