title: Supplementation of Mice with Specific Nondigestible Oligosaccharides during Pregnancy or Lactation Leads to Diminished Sensitization and Allergy in the Female Offspring.
abstract: BACKGROUND
  The maternal environment and early life exposure affect immune development in offspring.
  
  
  OBJECTIVE
  We investigated whether development of food allergy in offspring is affected by supplementing pregnant or lactating sensitized or nonsensitized mice with a mixture of nondigestible oligosaccharides.
  
  
  METHODS
  Dams were sensitized intragastrically with ovalbumin before mating, with use of cholera toxin (CT) as an adjuvant. Nonsensitized dams received CT only. Dams were fed a control diet or a diet supplemented with short-chain galacto oligosaccharides (scGOSs), long-chain fructo oligosaccharides (lcFOSs), and pectin-derived acidic oligosaccharides (pAOSs) in a ratio of 9:1:2 at a dose of 2% during pregnancy or lactation, resulting in 7 experimental groups. After weaning, offspring were fed a control diet and ovalbumin-CT sensitized. Acute allergic skin responses (ASRs), shock symptoms, body temperature, and specific plasma immunoglobulins were measured upon intradermal ovalbumin challenge. Th2/Th1- and regulatory T cells were analyzed with use of quantitative polymerase chain reaction and flow cytometric analysis in spleen, mesenteric lymph nodes, and blood.
  
  
  RESULTS
  Supplementing sensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower ASRs in the offspring [offspring of sensitized female mice fed experimental diet during pregnancy (S-Preg): 48 ± 2.1 μm; offspring of sensitized female mice fed experimental diet during lactation (S-Lact): 60 ± 6.2 μm] compared with the sensitized control group (119 ± 13.9 μm). In the S-Lact group, this coincided with an absence of shock symptoms compared with the offspring of sensitized female mice fed control food during pregnancy and lactation (S-Con) and S-Preg groups, and lower ovalbumin-IgG1 [S-Con: 3.8 ± 0.1 arbitrary units (AUs); S-Preg: 3.3 ± 0.1 AUs; S-Lact: 2.4 ± 0.1 AUs] and higher ovalbumin-IgG2a concentrations (S-Con: 1.1 ± 0.1 AUs; S-Preg: 0.8 ± 0.1 AUs; S-Lact: 2.0 ± 0.1 AUs). Supplementing nonsensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower plasma ovalbumin-IgE [offspring of nonsensitized female mice fed experimental diet during pregnancy (NS-Preg): 1.6 ± 0.4 AUs; offspring of nonsensitized female mice fed experimental diet during lactation (NS-Lact): 0.3 ± 0.1 AUs vs. offspring of nonsensitized female mice fed control food during pregnancy and lactation (NS-Con): 3.1 ± 0.6 AUs] and ovalbumin-IgG1 (NS-Lact: 2.3 ± 0.3 AUs vs. NS-Con: 3.4 ± 0.3 AUs) concentrations in offspring. Ovalbumin-IgG2a plasma concentrations were higher in offspring of scGOS/lcFOS/pAOS-supplemented dams (NS-Preg: 1.1 ± 0.1 AUs; NS-Lact: 1.1 ± 0.1 AUs) than in those of unsupplemented, nonsensitized controls (0.4 ± 0.0 AUs).
  
  
  CONCLUSIONS
  These data show impaired sensitization in offspring of scGOS/lcFOS/pAOS-supplemented mice. A number of the analyzed variables are differentially affected by whether supplementation occurs during pregnancy or lactation, and the outcome of dietary supplementation is affected by whether the mother has been sensitized to ovalbumin and CT.
authors.affiliation: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; and A.Hogenkamp@uu.nl.
authors.forename: Astrid
authors.initials: A
authors.lastname: Hogenkamp
authors.affiliation: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; and Nutricia Research, Utrecht, The Netherlands.
authors.forename: Leon M J
authors.initials: LM
authors.lastname: Knippels
authors.affiliation: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; and Nutricia Research, Utrecht, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.affiliation: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; and Nutricia Research, Utrecht, The Netherlands.
authors.forename: Betty C A M
authors.initials: BC
authors.lastname: van Esch
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D004043:Dietary Fiber / Q000627:therapeutic use*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D021181:Egg Hypersensitivity / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D047109:Fetal Development; D007073:Immunoglobulin E / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007774:Lactation; D039382:Maternal Nutritional Physiological Phenomena; D008809:Mice, Inbred C3H; D009844:Oligosaccharides / Q000627:therapeutic use*; D010047:Ovalbumin; D011247:Pregnancy; D011897:Random Allocation; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D004043:Dietary Fiber; D007074:Immunoglobulin G; D009844:Oligosaccharides; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: food allergy; hen’s egg; maternal dietary intervention; oligosaccharides; programming