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一种益生菌通过降低结合型胆汁酸来靶向胆汁酸代谢以缓解溃疡性结肠炎。

A Probiotic Targets Bile Acids Metabolism to Alleviate Ulcerative Colitis by Reducing Conjugated Bile Acids.

机构信息

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, 730000, P. R. China.

Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, P. R. China.

出版信息

Mol Nutr Food Res. 2024 Apr;68(7):e2300731. doi: 10.1002/mnfr.202300731. Epub 2024 Mar 13.

Abstract

SCOPE

Gut microbiota (GM) dysbiosis and dysregulated bile acids (BAs) metabolism have been linked to ulcerative colitis (UC) pathogenesis. The possibility of utilizing live probiotics with a defined BAs-metabolizing capability to modify the composition BAs for UC treatment remains unexplored.

METHODS AND RESULTS

In this study, Strain GR-4 is sourced from traditional Chinese fermented food, "Jiangshui," and demonstrated the ability to deconjugate two common conjugated BAs by over 69% and 98.47%, respectively. It administers strain GR-4 to dextran sulfate sodium (DSS)-induced UC mice, and observes an overall alleviation of UC symptoms, as evidence by improved colon morphology, reduces inflammation and oxidative stress, and restores intestinal barrier function. Importantly, these effects are reliant on an intact commensal microbiota, as depletion of GM mitigated GR-4s efficacy. Metabolomics analysis unveils a decline in conjugated BAs and an increase in secondary BAs following GR-4 administration. GM analysis indicates that GR-4 selectively enriches bacterial taxa linked to BAs metabolism, enhancing GM's capacity to modify BAs.

CONCLUSION

This research demonstrates the potential for natural fermented foods and probiotics to effectively manipulate BAs composition, including conjugated and secondary BAs, to alleviate UC symptoms, underscoring the benefits of these approaches for gut health.

摘要

范围

肠道微生物群(GM)失调和胆汁酸(BAs)代谢失调与溃疡性结肠炎(UC)的发病机制有关。利用具有特定 BAs 代谢能力的活菌来改变 BAs 组成以治疗 UC 的可能性尚未得到探索。

方法和结果

在这项研究中,GR-4 菌株来源于中国传统发酵食品“姜汁水”,并表现出分别超过 69%和 98.47%的去共轭两种常见共轭 BAs 的能力。它给葡聚糖硫酸钠(DSS)诱导的 UC 小鼠施用 GR-4 菌株,并观察到 UC 症状的整体缓解,表现为结肠形态改善、炎症和氧化应激减轻以及肠道屏障功能恢复。重要的是,这些作用依赖于完整的共生微生物群,因为 GM 的耗竭减轻了 GR-4 的功效。代谢组学分析显示,GR-4 给药后共轭 BAs 下降,次级 BAs 增加。GM 分析表明,GR-4 选择性地富集与 BAs 代谢相关的细菌分类群,增强 GM 修饰 BAs 的能力。

结论

这项研究表明,天然发酵食品和益生菌有可能有效地操纵 BAs 组成,包括共轭和次级 BAs,以缓解 UC 症状,强调了这些方法对肠道健康的益处。

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