title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands; and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands r.m.mariman@gmail.com.
authors.forename: Rob
authors.initials: R
authors.lastname: Mariman
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands; and.
authors.forename: Frans
authors.initials: F
authors.lastname: Tielen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands; and.
authors.forename: Lex
authors.initials: L
authors.lastname: Nagelkerken
mesh_terms: D000818:Animals; D001644:Bifidobacterium; D015169:Colony Count, Microbial; D003713:Dendritic Cells / Q000378:metabolism; D015536:Down-Regulation; D047209:Eosinophil Peroxidase / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D007778:Lactobacillus; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D064307:Microbiota; D010581:Peyer's Patches / Q000378:metabolism; D019936:Probiotics / Q000008:administration & dosage*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000592874:CCR5 protein, mouse; C515188:Cxcr3 protein, mouse; C508440:Il12rb1 protein, mouse; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D053707:Receptors, Interleukin-12; D047209:Eosinophil Peroxidase
keywords: flow cytometry; host genetics; immune modulation; microarray; probiotics