title: In vitro evaluation of defined oligosaccharide fractions in an equine model of inflammation.
abstract: BACKGROUND
  Dietary supplementation with oligosaccharides has been proven to be beneficial for health in several mammalian species. Next to prebiotic effects resulting in a modulation of gut micro biota, immunomodulatory effects of oligosaccharides have been documented in vivo. Supplementation with defined oligosaccharide fractions has been shown to attenuate allergic responses and enhance defensive immune responses. Despite the accumulating evidence for immunomodulatory effects, very limited information is available regarding the direct mechanism of action of oligosaccharides. This study aims to elucidate the effects of selected oligosaccharide fractions on the lipopolysaccharide (LPS) induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). We investigated three different products containing either galacto-oligosaccharides (GOS) alone, a combination of GOS with fructo-oligosaccharides (FOS), and a triple combination of GOS and FOS with acidic oligosaccharides (AOS), at different concentrations. These products have been used in an identical composition in various previously published in vivo experiments. As the selected oligosaccharide fractions were derived from natural products, the fractions contained defined amounts of mono- and disaccharides and minor amounts of endotoxin, which was taken into account in the design of the study and the analysis of data. Acquired data were analysed in a Bayesian hierarchical linear regression model, accounting for variation between horses.
  
  
  RESULTS
  Exposing cultured PBMCs to either GOS or GOS/FOS fractions resulted in a substantial dose-dependent increase of tumour necrosis factor-α (TNF-α) production in LPS challenged PBMCs. In contrast, incubation with GOS/FOS/AOS resulted in a dose-dependent reduction of both TNF-α and interleukin-10 production following LPS challenge. In addition, incubation with GOS/FOS/AOS significantly increased the apparent PBMC viability, indicating a protective or mitogenic effect. Furthermore, mono- and disaccharide control fractions significantly stimulated the inflammatory response in LPS challenged PBMCs as well, though to a lesser extent than GOS and GOS/FOS fractions.
  
  
  CONCLUSIONS
  We found distinct immunomodulating effects of the investigated standardised oligosaccharide fractions, which either stimulated or suppressed the LPS induced inflammatory response in PBMCs. Both scenarios require additional investigation, to elucidate underlying modulatory mechanisms, and to translate this knowledge into the clinical application of oligosaccharide supplements in foals and other neonates.
authors.affiliation: Department of Veterinary Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, P,O, box 80152, 3508, TD Utrecht, The Netherlands. J.C.Vendrig@uu.nl
authors.forename: Johannes Cornelis
authors.initials: JC
authors.lastname: Vendrig
authors.forename: Luc Edgar
authors.initials: LE
authors.lastname: Coffeng
authors.forename: Johanna
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006734:Horse Diseases / Q000276:immunology* / Q000378:metabolism; D006736:Horses; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D016014:Linear Models; D008070:Lipopolysaccharides; D009010:Monte Carlo Method; D009844:Oligosaccharides / Q000494:pharmacology*; D056692:Prebiotics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D056692:Prebiotics; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D016753:Interleukin-10