Department of Veterinary Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, P,O, box 80152, 3508, TD Utrecht, The Netherlands.
BMC Vet Res. 2013 Jul 22;9:147. doi: 10.1186/1746-6148-9-147.
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.
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.
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.
在许多哺乳动物物种中,膳食补充低聚糖已被证明对健康有益。除了导致肠道微生物群改变的益生元作用外,低聚糖的免疫调节作用在体内也有记录。用定义明确的低聚糖分数进行补充已被证明可以减轻过敏反应并增强防御性免疫反应。尽管有越来越多的证据表明具有免疫调节作用,但关于低聚糖的直接作用机制的信息非常有限。本研究旨在阐明选定的低聚糖分数对马外周血单核细胞(PBMC)中脂多糖(LPS)诱导的炎症反应的影响。我们研究了三种不同的产品,它们分别含有单独的半乳糖低聚糖(GOS),GOS 与果低聚糖(FOS)的混合物,以及 GOS 和 FOS 与酸性低聚糖(AOS)的三重混合物,浓度不同。这些产品在以前发表的各种体内实验中以相同的成分使用。由于所选的低聚糖分数来自天然产物,因此这些分数包含一定量的单糖和二糖以及少量内毒素,在研究设计和数据分析中考虑到了这一点。获取的数据在贝叶斯分层线性回归模型中进行分析,考虑了马之间的差异。
将培养的 PBMC 暴露于 GOS 或 GOS/FOS 分数中,会导致 LPS 刺激的 PBMC 中肿瘤坏死因子-α(TNF-α)产生的剂量依赖性增加。相比之下,与 GOS/FOS/AOS 孵育会导致 LPS 挑战后 TNF-α和白细胞介素-10 的产生呈剂量依赖性降低。此外,GOS/FOS/AOS 的孵育显着增加了 PBMC 的表观活力,表明具有保护或有丝分裂作用。此外,单糖和二糖对照分数也显着刺激了 LPS 刺激的 PBMC 中的炎症反应,尽管程度低于 GOS 和 GOS/FOS 分数。
我们发现研究的标准化低聚糖分数具有明显的免疫调节作用,可刺激或抑制 PBMC 中 LPS 诱导的炎症反应。这两种情况都需要进一步研究,以阐明潜在的调节机制,并将这一知识转化为低聚糖补充剂在小马驹和其他新生儿中的临床应用。