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高剂量的低聚半乳糖、2'-岩藻糖基乳糖可在体内外缓解免疫缺陷。

High doses of the galactooligosaccharides, 2'-fucosyllactose alleviate immunodeficiency in vitro and in vivo.

作者信息

Li Xiaxia, Li Yao, Cheng Kang, Song Tao, Wang Yi, Zhou Haolin, Xu Yafang, Chaibou Oumarou Zafir, Wang Bing, Li Huajun

机构信息

Department of Pathogen Biology and Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.

出版信息

Eur J Nutr. 2025 Jun 9;64(5):215. doi: 10.1007/s00394-025-03734-6.

DOI:10.1007/s00394-025-03734-6
PMID:40488907
Abstract

PURPOSE

Galactooligosaccharides (GOS) are widely added to infant formula milk powder. One of these, 2'-fucosyllactose (2'-FL), has many potential applications. This study investigated the immunomodulatory effects of GOS and 2'-FL, alone or in combination, on RAW 264.7 cells, and their impacts on cyclophosphamide (CTX)-induced immunodeficiency in mice.

METHODS

We used lipopolysaccharide (LPS)-treated RAW 264.7 cells and CTX-induced immunodeficient model mice to analyze the effects of GOS, 2'-FL, and the combination GOSFL on apparent indicators, cellular immunity, inflammation, intestinal barrier function, and the gut microbiota and its metabolites.

RESULTS

In vitro, GOS and 2'-FL promoted cell proliferation and nitric oxide production, and exhibited dose-dependent increases in the secretion of interleukin-10 (IL)-10, IL-6, and tumor necrosis factor-α. In vivo, high-dose administration GOS, 2'-FL, or GOSFL reduced the body weight and spleen index of immune-deficient mice, increased the number of splenic immune cells, alleviated inflammation, and promoted the expression of Occludin, ZO-1, and MUC2 to restore the intestinal mucosal barrier. GOS and 2'-FL each increased the relative abundances of Bacteroidota and Muribaculaceae, while decreasing those of Firmicutes, Lachnospiraceae, and Lactobacillaceae. Spearman correlation analysis revealed correlations between the gut microbiota and serum immune factors, as well as short-chain fatty acids.

CONCLUSION

GOS and 2'-FL significantly promoted cytokine secretion in vitro. High doses of GOS or 2'-FL in vivo reversed the adverse effects induced by CTX, modulated the gut microbiota, and boosted the immune response, with combination use producing similar effects.

摘要

目的

低聚半乳糖(GOS)被广泛添加到婴儿配方奶粉中。其中一种,2'-岩藻糖基乳糖(2'-FL),有许多潜在应用。本研究调查了GOS和2'-FL单独或联合使用对RAW 264.7细胞的免疫调节作用,以及它们对环磷酰胺(CTX)诱导的小鼠免疫缺陷的影响。

方法

我们使用脂多糖(LPS)处理的RAW 264.7细胞和CTX诱导的免疫缺陷模型小鼠,来分析GOS、2'-FL以及GOS与2'-FL的组合(GOSFL)对表观指标、细胞免疫、炎症、肠道屏障功能以及肠道微生物群及其代谢产物的影响。

结果

在体外,GOS和2'-FL促进细胞增殖和一氧化氮生成,并呈现白细胞介素-10(IL)-10、IL-6和肿瘤坏死因子-α分泌的剂量依赖性增加。在体内,高剂量给予GOS、2'-FL或GOSFL可降低免疫缺陷小鼠的体重和脾脏指数,增加脾脏免疫细胞数量,减轻炎症,并促进闭合蛋白、紧密连接蛋白1和黏蛋白2的表达以恢复肠道黏膜屏障。GOS和2'-FL各自增加了拟杆菌门和毛螺菌科的相对丰度,同时降低了厚壁菌门、瘤胃球菌科和乳杆菌科的相对丰度。Spearman相关性分析揭示了肠道微生物群与血清免疫因子以及短链脂肪酸之间的相关性。

结论

GOS和2'-FL在体外显著促进细胞因子分泌。体内高剂量的GOS或2'-FL可逆转CTX诱导的不良反应,调节肠道微生物群,并增强免疫反应,联合使用产生类似效果。

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