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理中汤通过调节肠道微生物群-短链脂肪酸-Th17/调节性T细胞轴减轻实验性溃疡性结肠炎。

Lizhong decoction alleviates experimental ulcerative colitis via regulating gut microbiota-SCFAs-Th17/Treg axis.

作者信息

Huang Hengjun, Yang Chengyu, Li Silu, Zhan Huang, Tan Jinlong, Chen Congcong, Liu Jian, Wang Maolin, Li Hui

机构信息

Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, 330115, China; Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang, 330115, China.

Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, 330115, China; Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang, 330115, China.

出版信息

J Ethnopharmacol. 2025 Jun 12;349:119958. doi: 10.1016/j.jep.2025.119958. Epub 2025 May 9.

DOI:10.1016/j.jep.2025.119958
PMID:40350047
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Lizhong decoction (LZD), a Traditional Chinese Medicine formula, is widely utilized to treat gastrointestinal diseases, including ulcerative colitis in China for thousands of years.

AIM OF THE STUDY

To investigate whether the protective effect of LZD on ulcerative colitis is dependent on gut microbiota and T-cell immune homeostasis.

MATERIAL AND METHODS

The preventive effects of LZD on dextran sodium sulfate (DSS)-induced colitis mice were evaluated through the measurement of body weight, disease activity index, colon length and hematoxylin-eosin staining. Flow cytometry was used to detect the ratio of Th17/Treg cells. Pseudo sterile mice and fecal transplantation experiments were used to investigate whether the preventive effect of LZD was dependent on the gut microbiota. The alterations of gut microbiota were identified by the 16S rDNA sequencing. The content of intestinal short-chain fatty acids (SCFAs) was detected by LC-MS/MS analysis. The downstream signal pathways of SCFAs were detected by the immunoblotting.

RESULTS

LZD administration significantly alleviated weight loss and intestinal injury in DSS-induced colitis mice. LZD administration also promotes the balance of Th17/Treg cells. Moreover, LZD administration relies on gut microbiota to alleviate ulcerative colitis and regulate Th17/Treg cell balance. LZD administration significantly improves gut microbial composition in colitis mice, elevating the abundance of SCFAs producing bacterium such as lachnospiraceae_nk4a136_group and Akkermansia. LZD treatment further increases the abundance of SCFAs and promotes activation of free fatty acid activated receptor 2 (FFAR2).

CONCLUSION

LZD administration promotes Th17/Treg cell balance in a gut microbiota-SCFAs dependent manner, which in turn ameliorates ulcerative colitis.

摘要

民族药理学相关性

理中汤(LZD)是一种中药配方,在中国已被广泛用于治疗胃肠道疾病,包括溃疡性结肠炎,已有数千年历史。

研究目的

探讨理中汤对溃疡性结肠炎的保护作用是否依赖于肠道微生物群和T细胞免疫稳态。

材料与方法

通过测量体重、疾病活动指数、结肠长度和苏木精-伊红染色,评估理中汤对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠的预防作用。采用流式细胞术检测Th17/Treg细胞比例。利用伪无菌小鼠和粪便移植实验研究理中汤的预防作用是否依赖于肠道微生物群。通过16S rDNA测序鉴定肠道微生物群的变化。采用液相色谱-串联质谱分析检测肠道短链脂肪酸(SCFA)的含量。通过免疫印迹检测SCFA的下游信号通路。

结果

给予理中汤可显著减轻DSS诱导的结肠炎小鼠的体重减轻和肠道损伤。给予理中汤还可促进Th17/Treg细胞的平衡。此外,给予理中汤依赖肠道微生物群来减轻溃疡性结肠炎并调节Th17/Treg细胞平衡。给予理中汤可显著改善结肠炎小鼠的肠道微生物组成,提高产SCFA细菌如毛螺菌科_nk4a136_组和阿克曼氏菌的丰度。理中汤治疗进一步增加了SCFA的丰度,并促进了游离脂肪酸激活受体2(FFAR2)的激活。

结论

给予理中汤以肠道微生物群-SCFA依赖的方式促进Th17/Treg细胞平衡,进而改善溃疡性结肠炎。

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