唾液酸化IgG对肠道菌群的调节作用及机制研究

Sialylated IgG is an important immunoglobulin in breast milk, but its effect on gut microbiota is not yet clear. The latest research has showed that glycoproteins and oligosaccharides containing sialic acids have an important influence on the gut microbiota, and the gut microbiota has genes related to the hydrolysis and transport of α2,6-linked sialic acid and β1,4-linked galactose. Meanwhile, our previous study has delivered the intact IgG to the gut and showd that the gut microbiota reduced the retention of sialylated IgG. Therefore, it is presumed that the single gut microbiota will hydrolysis and transport the heterogeneous sugar at the end of sugar chain to regulate the structure of gut microbiota. Based on this, we will explore the dose and time effects of sialylated IgG on gut microbiota structure through anaerobic fermentation in vitro of intestinal microflora in the project. Furthermore, the dominant strains responded significantly to sialylated IgG will be identified and the metabolic network of end-heterogeneous sugars of sialylated IgG will be built under levels of physiology and biochemistry, gene expression and proteome. The study result will elucidate the mechanism of sialylated IgG effect as natural food additives on gut microbiota structure. It will also provide new ways and theoretical guidance for the evaluation of biopotency of immunoglobulins in breast milk.

唾液酸化IgG是母乳中重要的免疫球蛋白，但其对肠道菌群的调节作用尚不明确。最新的研究发现含有唾液酸的糖蛋白及寡糖对肠道菌群有着重要影响，而且肠道菌群具有水解及转运α2,6键连接的唾液酸和β1,4键连接的半乳糖的相关基因。我们前期研究已将IgG完整地投递至肠道，并发现肠道菌群会降低唾液酸化IgG的保留率。因此推测唾液酸化IgG会因其末端异质性糖的肠道单菌水解转运作用影响肠道菌群结构。本课题拟通过构建肠道菌群体外厌氧发酵模型，分析唾液酸化IgG对肠道菌群结构影响的剂量效应和时间效应，定向挖掘并分离鉴定对唾液酸化IgG有显著响应的菌株，进一步通过生理生化、转录组学和蛋白组学三个层面系统解析唾液酸化IgG末端异质性糖的单菌水解及转运作用，阐明唾液酸化IgG作为天然食品添加剂对肠道菌群结构影响机制，为母乳中免疫球蛋白类的生物效价鉴评提供新的途径和理论指导。

α2,6唾液酸IgG是母乳中重要的具有抗炎活性的免疫球蛋白，但已有研究忽视了其作为天然食品添加剂对肠道菌群的调节效应。本项目通过构建人源肠道菌群体外厌氧发酵模型，结合生理生化、基因转录和糖组学三个层面揭示α2,6唾液酸IgG对肠道菌群结构的调节效应及机制。研究结果表明α2,6唾液酸IgG促进成人肠道增殖三种只在母乳喂养的婴幼儿肠道中常见的双歧菌株B. bifidum CCX 19061、B. breve CCX 19041和B. longum subsp. infantis CCX 19042，其中B. breve CCX 19041和B. longum subsp. infantis CCX 19042主要利用B. bifidum CCX 19061分泌的胞外酶从α2,6唾液酸化IgG的N-聚糖释放的单糖作为碳源进行生长繁殖。此外，研究还发现α2,6唾液酸化IgG可以通过促进双歧杆菌增殖进而缓解结肠炎症状并阐释了其作用机制，同时建立了以动物源唾液酸化IgG为基质对其进行人源化转化方法。研究结果为α2,6唾液酸IgG的利用与健康产品的开发提供了全新的视角和重要科学依据，尤其为母乳中免疫球蛋白类的生物效价鉴评提供新的途径和理论指导。