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基于四菌株益生菌组合的合生元体外筛选及其对溃疡性结肠炎的治疗潜力

In vitro screening of synbiotics based on a four-strain probiotic blend and their therapeutic potential for ulcerative colitis.

作者信息

Liao Jiahao, Guo Ying, Guo Zhuoya, Zhang Xianqian, Li Xiaoqiong, Kuang Jian, Li Jianqiang, Bian Xiangyu, Wang Weiwei, Li Jinjun

机构信息

Key Laboratory of Postharvest Preservation and Processing of Vegetables (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory of Intelligent Food Logistic and Processing, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China; College of Animal Science, Shanxi Agricultural University, Taigu 030801, China.

Key Laboratory of Postharvest Preservation and Processing of Vegetables (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory of Intelligent Food Logistic and Processing, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.

出版信息

Biomed Pharmacother. 2025 Oct;191:118521. doi: 10.1016/j.biopha.2025.118521. Epub 2025 Sep 3.

DOI:10.1016/j.biopha.2025.118521
PMID:40907171
Abstract

This study explores the therapeutic effects of synbiotics on ulcerative colitis (UC) using an in vitro fermentation model and a Dextran Sulfate Sodium (DSS)-induced UC mouse model. We assessed the impact of synbiotics on probiotic proliferation, short-chain fatty acid (SCFA) production, metabolic regulation, and intestinal barrier function. Fructooligosaccharide (FOS) and Inulin (INU) significantly promoted probiotic growth and increased SCFA production, especially acetate, propionate, butyrate, and isobutyrate (p < 0.01). Metabolomics analysis revealed compound probiotics (CP)+FOS and CP+INU significantly modulated probiotic metabolic activity (p < 0.05), affecting metabolites and related pathways. In the DSS-induced UC mouse model, the combination of CP+FOS and CP+INU alleviated UC symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while increasing spleen index. Histological analysis showed synbiotics preserved colonic crypts, reduced inflammatory cell infiltration, and enhanced intestinal barrier function, with the CP+FOS group showing the most pronounced effects. Immunohistochemistry revealed restored expression of tight junction proteins (Claudin-1, Occludin, ZO-1), further supporting intestinal barrier protection. The synbiotic combination modulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory IL-10 (p < 0.01). SCFA analysis showed significant increases in all measured SCFAs (p < 0.01). Correlation analysis indicated strong positive associations between SCFAs, body weight, colon length, and IL-10. In conclusion, the synbiotic combination of FOS and INU shows significant potential in alleviating UC symptoms, repairing the intestinal barrier, and modulating inflammation, supporting its potential as an adjunct or alternative UC therapy.

摘要

本研究使用体外发酵模型和葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠模型,探讨了合生元对溃疡性结肠炎的治疗效果。我们评估了合生元对益生菌增殖、短链脂肪酸(SCFA)产生、代谢调节和肠道屏障功能的影响。低聚果糖(FOS)和菊粉(INU)显著促进了益生菌生长并增加了SCFA的产生,尤其是乙酸、丙酸、丁酸和异丁酸(p<0.01)。代谢组学分析显示,复合益生菌(CP)+FOS和CP+INU显著调节了益生菌的代谢活性(p<0.05),影响了代谢物和相关途径。在DSS诱导的UC小鼠模型中,CP+FOS和CP+INU的组合减轻了UC症状,包括体重减轻、疾病活动指数(DAI)评分和结肠缩短,同时增加了脾脏指数。组织学分析表明,合生元保留了结肠隐窝,减少了炎性细胞浸润,并增强了肠道屏障功能,其中CP+FOS组的效果最为明显。免疫组织化学显示紧密连接蛋白(Claudin-1、Occludin、ZO-1)的表达得以恢复,进一步支持了对肠道屏障的保护作用。合生元组合调节了促炎细胞因子(IL-1β、IL-6、TNF-α)并增加了抗炎性IL-10(p<0.01)。SCFA分析显示,所有测量的SCFA均显著增加(p<0.01)。相关性分析表明,SCFA、体重、结肠长度和IL-10之间存在强正相关。总之,FOS和INU的合生元组合在减轻UC症状、修复肠道屏障和调节炎症方面显示出显著潜力,支持其作为UC辅助或替代疗法的潜力。

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