苜蓿多糖通过调节肠道菌群和肠道屏障对抗TLR4/MyD88/NF-κB通路缓解结肠炎

IF 5 2区 医学 Q1 NUTRITION & DIETETICS
Nutrients Pub Date : 2025-09-19 DOI:10.3390/nu17183001
Shaokai La, Muhammad Abaidullah, Hao Li, Yalei Cui, Boshuai Liu, Yinghua Shi
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引用次数: 0

摘要

背景/目的:溃疡性结肠炎(UC)的发病机制涉及肠道屏障功能障碍、免疫反应失调和肠道菌群失衡。苜蓿多糖(APS)是一种具有免疫调节潜力的生物活性化合物,在肠道炎症中的作用尚未得到充分的研究。虽然APS在体外表现出抗炎特性,但其在UC中的体内功效、机制和恢复肠道微生物群和屏障完整性的能力尚不清楚。本研究旨在探讨黄芪多糖对葡聚糖硫酸钠(DSS)诱导小鼠结肠炎的治疗作用,并证实其益生元潜力。方法:采用DSS诱导小鼠溃疡性结肠炎模型。采用RNA测序、Western blotting、末端脱氧核苷酸转移酶dUTP刻痕末端标记技术和免疫组织化学技术研究不同剂量APS缓解dss诱导结肠炎的作用机制。结果:黄芪多糖可减轻DSS小鼠结肠炎症状,改善肠道形态,增加杯状细胞生成,提高IL-10和IL-22水平,降低TNF-α、IL-1β和IL-6水平,阻止TLR4/MyD88/NF-κB通路的激活。此外,它们通过增强粘蛋白MUC2和MUC5AC的表达以及增加ZO-1、Occludin和Claudin-1蛋白的量来维持肠道的完整性。此外,APS支持益生菌的生长,包括unclassified_f_lachnospiraceae, Parabacteroides, Alistipes和Mucispirillum,特别是Parabacteroides distasonis,其通过抑制TLR4-MyD88-NFκB通路与促炎细胞因子的降低密切相关。结论:APS可作为一种新型益生元,通过调节肠道菌群,增强肠道屏障功能,对抗TLR4-MyD88-NFκB通路,改善UC。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Alfalfa Polysaccharide Alleviates Colitis by Regulating Intestinal Microbiota and the Intestinal Barrier Against the TLR4/MyD88/NF-κB Pathway.

Background/Objectives: Ulcerative colitis (UC) pathogenesis involves gut barrier dysfunction, dysregulated immune responses, and gut microbiota imbalance. Alfalfa polysaccharide (APS), a bioactive compound with immunomodulatory potential, remains underexplored in intestinal inflammation. While APS exhibits anti-inflammatory properties in vitro, its in vivo efficacy, mechanisms, and ability to restore gut microbiota and barrier integrity in UC are unclear. This study aims to investigate the treatment effect of APS on dextran sulfate sodium (DSS)-induced colitis in mice and confirm its prebiotic potential. Methods: A mouse model of ulcerative colitis was induced by DSS. RNA sequencing, Western blotting, the terminal deoxynucleotidyl transferase dUTP nick end labeling technique, and an immuno-histochemical technique were used to study the mechanism of action by which APS at different dosages relieves DSS-induced colitis. Results: The findings show that APS alleviated the symptoms of colitis in mice given DSS, improved the gut morphology, heightened goblet cells production, increased the levels of IL-10 and IL-22, decreased the levels of TNF-α, IL-1β, and IL-6, and prevented the activation of the TLR4/MyD88/NF-κB pathways. Additionally, they maintained the integrity of the intestine by enhancing the expression of the mucins MUC2 and MUC5AC and by increasing the amounts of ZO-1, Occludin, and Claudin-1 proteins. Moreover, APS supported the growth of probiotic bacteria, including unclassified_f_lachnospiraceae, Parabacteroides, Alistipes, and Mucispirillum, and in particular, Parabacteroides distasonis, which is strongly associated with decreased pro-inflammatory cytokine through the inhibition of the TLR4-MyD88-NFκB pathways. Conclusions: APS can be used as a new type of prebiotic to improve UC by regulating intestinal flora and enhancing intestinal barrier function against the TLR4-MyD88-NFκB pathway.

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来源期刊
Nutrients
Nutrients NUTRITION & DIETETICS-
CiteScore
9.20
自引率
15.30%
发文量
4599
审稿时长
16.74 days
期刊介绍: Nutrients (ISSN 2072-6643) is an international, peer-reviewed open access advanced forum for studies related to Human Nutrition. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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