食品科学 ›› 2024, Vol. 45 ›› Issue (14): 103-113.doi: 10.7506/spkx1002-6630-20231018-145

• 营养卫生 • 上一篇    下一篇

N-羟乙酰神经氨酸通过调节肠道菌群致小鼠的炎症机制

贺乐丽, 刘楚鑫, 肖毅, 沈清武, 吴艳阳   

  1. (湖南农业大学食品科学技术学院, 食品科学与生物技术湖南省重点实验室, 湖南 长沙 410128)
  • 出版日期:2024-07-25 发布日期:2024-08-04
  • 基金资助:
    国家自然科学基金面上项目(32072334;31771992)

Proinflammatory Mechanism of N-Glycolylneuraminic Acid in Mice through Regulating the Gut Microbiota

HE Leli, LIU Chuxin, XIAO Yi, SHEN Qingwu, WU Yanyang   

  1. (Hunan Province Key Laboratory of Food Science and Biotechnology, School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China)
  • Online:2024-07-25 Published:2024-08-04

摘要: 本研究以CMP-Neu5Ac羟化酶敲除(cytidine-5’-monophosphate-N-acetylneuraminic acid knockout, Cmah-/-)小鼠为对象, 将猪颌下腺黏蛋白(porcine submaxillary gland mucin, PSM)中的N-羟乙酰神经氨酸(N-glycolylneuraminic acid, Neu5Gc)添加到小鼠饲料中, 饮食干预18 周后探究Neu5Gc对Cmah-/-小鼠肝脏中核因子κB(nuclear factor kappa-B, NF-κB)信号通路相关蛋白和血清中白细胞介素(interleukin, IL)-6、IL-1β、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)与血清淀粉样蛋白A(serum amyloid A protein, SAA)以及肠道菌群的影响, 并分析不同性别对Neu5Gc致Cmah-/-小鼠炎症的影响。结果表明, 与普通对照组相比, PSM中的Neu5Gc激活了NF-κB信号通路, 显著增加了雄鼠和雌鼠血清中IL-6、IL-1β、TNF-α和SAA的质量浓度;PSM雄鼠处理组中的Bacteroidetes和Firmicutes的相对丰度比值显著升高, Muribaculaceae和Prevotellaceae显著下降, Clostridia UCG-014和Prevotellaceae_NK3B31_group等与肠道炎症呈正相关菌群的相对丰度显著升高;PSM雌鼠处理组中的肠道菌群的丰富度显著减少, Lachnospiraceae和Oscillospiraceae的相对丰度显著下降。综上, PSM中的Neu5Gc可能通过显著下调相关菌群丰度, 促进与肠道炎症呈正相关的菌群生长, 导致肠道菌群结构紊乱, 激活NF-κB信号通路, 增加小鼠血清炎性细胞因子的分泌, 从而促进Cmah-/-小鼠体内炎症反应, 且其致小鼠炎症受性别因素的影响。本研究阐明了膳食红肉的致炎症反应机制, 为人们的饮食健康提供了一定的参考。

关键词: N-羟乙酰神经氨酸;炎性细胞因子;肠道菌群;性别差异;慢性炎症

Abstract: In this study, the effect of 18 weeks of dietary supplementation of porcine submaxillary gland mucin (PSM) as an abundant source of N-hydroxyacetylneuraminic acid (Neu5Gc) on the expression of proteins involved in the nuclear factor kappa-B (NF-κB) signaling pathway in the liver, serum interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α), serum amyloid A protein (SAA) and the gut microbiota in cytidine-5’-monophosphate-N-acetylneuraminic acid knockout (Cmah-/-) mice was investigated. Meanwhile, the effect of gender on Neu5Gc-induced inflammation in Cmah-/- mice was analyzed. The results showed that Neu5Gc activated the NF-κB signaling pathway and significantly increased the serum concentration of IL-6, IL-1β, TNF-α and SAA in both male and female mice when compared with normal controls. In the PSM-treated male mice, the ratio of Bacteroidetes to Firmicutes (B/F) significantly increased, the relative abundance of Muribaculaceae and Prevotellaceae significantly decreased, and the relative abundance of Clostridia UCG-014 and Prevotellaceae_NK3B31_group, which are positively associated with intestinal inflammation, significantly increased. In the PSM-treated female mice, the richness of gut microbiota significantly decreased, and so did the relative abundance of Lachnospiraceae and Oscillospiraceae. In conclusion, Neu5Gc in PSM could promote inflammatory responses in Cmah-/- mice through significantly down-regulating the abundance of relevant bacterial communities, facilitating the growth of bacterial communities positively associated with intestinal inflammation, leading to structural disorders of gut microbiota, activating the NF-κB signaling pathway and increasing the secretion of serum inflammatory cytokines, and inflammatory response induced in mice by Neu5Gc was affected by gender. Our study provides a reference for a healthy diet.

Key words: N-glycolylneuraminic acid; inflammatory cytokines; gut microbiota; sex differences; chronic inflammation

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