Journal of Reproductive Immunology 94 (2012) 161–168 Contents lists available at SciVerse ScienceDirect Journal of Reproductive Immunology j o ur nal homep age : w w w.elsevier.com/locate/jreprimm Effects of short-chain galacto- and long-chain fructo-oligosaccharides on systemic and local immune status during pregnancy  N. van Vlies a,1,2 , A. Hogenkamp a,1 , S. Thijssen a , G.M. Dingjan a,b , K. Knipping a,b , J. Garssen a,b , L.M.J. Knippels a,b,∗ a Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, The Netherlands b Immunology, Danone Research Centre for Specialised Nutrition, Wageningen, The Netherlands a r t i c l e i n f o Article history: Received 15 July 2011 Received in revised form 19 February 2012 Accepted 22 February 2012 Keywords: Prebiotics Galacto-oligosaccharide Fructo-oligosaccharide Pregnancy Delayed type hypersensitivity response Immune modulation a b s t r a c t Nondigestible oligosaccharides can positively influence health via various mechanisms. During pregnancy, supplementation of nondigestible oligosaccharides has positive effects on hypertension and metabolism and may be used to ameliorate pregnancy-related metabolic disturbances. In the nonpregnant state, nondigestible oligosaccharides have been shown to induce a tolerogenic immune response mediated by T-regulatory cells. Since rel- atively little is known about the effects of nondigestible oligosaccharides on the immune system during pregnancy, pregnant mice were supplemented with a specific mixture of short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS; ratio 9:1). Sys- temic and local immune parameters were analyzed on day 18 of pregnancy. This study shows that, compared with virgin mice, scGOS/lcFOS supplementation appears to elicit a more tolerogenic immune reaction in pregnant mice and supplementation does not increase the Th1-dependent delayed type hypersensitivity response in pregnant mice as it does in virgin mice. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The maternal immune system undergoes many adap- tations during pregnancy (Pearson, 2002). Although a Th2-type cytokine profile is important during pregnancy (Blois et al., 2004), it has become clear that the immune response is not merely shifted toward a Th2-dominated cytokine profile (Fallon et al., 2002), and it is now clear that many factors contribute to fetal immune evasion (Trowsdale and Betz, 2006). A critical role has been  Financial support: This study was financially supported by Danone Research Centre for Specialised Nutrition, Wageningen, The Netherlands. ∗ Corresponding author at: Danone Research, Bosrandweg 20, 6704PH Wageningen, The Netherlands. Tel.: +31 0 317 467800. E-mail address: leon.knippels@danone.com (L.M.J. Knippels). 1 Both authors contributed equally to this study. 2 Present address: Laboratory of Genetic Metabolic Disease, Academic Medical Centre, Amsterdam, The Netherlands. proposed for regulatory T cells (Tregs) in the generation of feto-maternal tolerance/hypo-responsiveness in mice (Aluvihare and Betz, 2006; Chaouat et al., 2010). Apart from T-cells, uterine NK (uNK) cells (Karimi and Arck, 2010) and macrophages (Renaud and Graham, 2008) play an important role during pregnancy, as they are key players in placental development and maintenance. The immune response of the newborn can also be affected by the maternal immune status during pregnancy, as this can prime the immune response in her offspring in utero. Maternal immune status is obviously not only depen- dent on changes that are caused by pregnancy, but also on external factors such as food quality/composition. In recent years, it has become clear that dietary compounds such as nondigestible oligosaccharides can exert beneficial immunomodulatory effects. Nondigestible oligosaccharides can influence the com- position and/or activity of the gastrointestinal microbiota, which confers benefits upon the host’s wellbeing and 0165-0378/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jri.2012.02.007