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The probiotic mixture VSL#3 has differential effects on intestinal immune parameters in healthy female BALB/c and C57BL/6 mice

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Author: Mariman, R. · Tielen, F. · Koning, F. · Nagelkerken, L.
Source:Journal of Nutrition, 6, 145, 1354-1361
Identifier: 526252
doi: doi:10.3945/jn.114.199729
Keywords: Biology · Flow cytometry · Host genetics · Immune modulation · Microarray · Probiotics · Chemokine receptor CCR5 · Chemokine receptor CXCR3 · Eosinophil peroxidase · Gamma interferon inducible protein 10 · Interleukin 12 receptor beta1 · Retinoid related orphan receptor gamma · Transcription factor GATA 3 · VSL3 · Adaptive immunity · Animal experiment · Colon · Controlled study · Female · Gene expression · Genetic variability · Homeostasis · Immunomodulation · Innate immunity · Intestine mucosa · Major histocompatibility complex · Mesentery lymph node · Microarray analysis · Mouse · Mouse strain · Nonhuman · Phenotype · Principal component analysis · Protein expression · Single drug dose · Small intestine · Upregulation · Mus · Biomedical Innovation · Healthy Living · Life · MHR - Metabolic Health Research · ELSS - Earth, Life and Social Sciences


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 × 108 colony-forming units of VSL#3. In a separate experiment in BALB/c mice, the effects of prolonged administration of VSL#3 and of phosphatebuffered saline (PBS), followed by 1 single dose of VSL#3, on innate and adaptive immune cells were evaluated. Results: Microarray analysis of the intestines ofmice treatedwith PBS confirmedwell-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/cmice but not in C57BL/6mice. 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) comparedwith 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 treatmentmediatesmouse 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. © 2015 American Society for Nutrition.