全面的微生物组学和粪便代谢组学结合网络药理学揭示了降脂通便胶囊对老年功能性便秘的作用。

Comprehensive microbiomes and fecal metabolomics combined with network pharmacology reveal the effects of Jichuanjian on aged functional constipation.

机构信息

Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist, Taiyuan 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan 030006, Shanxi, China; Institute of Biomedicine and Health, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist., Taiyuan 030006, Shanxi, China.

出版信息

Exp Gerontol. 2023 Jul;178:112216. doi: 10.1016/j.exger.2023.112216. Epub 2023 May 31.

DOI:10.1016/j.exger.2023.112216

PMID:37211069

Abstract

BACKGROUND

Functional constipation is a common gastrointestinal disorder especially severely affecting the life quality of the aged. Jichuanjian (JCJ) has been widely used for aged functional constipation (AFC) in clinic. Yet, the mechanisms of JCJ merely scratch the surface with being studied at a single level, rather than from a systematic perspective of the whole.

AIM

The purpose of this study was to explore the underlying mechanisms of JCJ in treating AFC from the perspectives of fecal metabolites and related pathways, gut microbiota, key gene targets and functional pathways, as well as "behaviors-microbiota-metabolites" relationships.

METHODS

16S rRNA analysis and fecal metabolomics combined with network pharmacology were applied to investigate the abnormal performances of AFC rats, as well as the regulatory effects of JCJ.

RESULTS

JCJ significantly regulated the abnormalities of rats' behaviors, the microbial richness, and the metabolite profiles that were interrupted by AFC. 19 metabolites were found to be significantly associated with AFC involving in 15 metabolic pathways. Delightfully, JCJ significantly regulated 9 metabolites and 6 metabolic pathways. AFC significantly interrupted the levels of 4 differential bacteria while JCJ significantly regulated the level of SMB53. HSP90AA1 and TP53 were the key genes, and pathways in cancer was the most relevant signaling pathways involving in the mechanisms of JCJ.

CONCLUSION

The current findings not only reveal that the occurrence of AFC is closely related to gut microbiota mediating amino acid and energy metabolism, but also demonstrate the effects and the underlying mechanisms of JCJ on AFC.

摘要

背景

功能性便秘是一种常见的胃肠道疾病，尤其严重影响老年人的生活质量。济川煎（JCJ）已广泛用于临床治疗老年功能性便秘（AFC）。然而，JCJ 的作用机制仅在单一水平上进行了研究，而不是从系统的角度进行研究。

目的

本研究旨在从粪便代谢物及相关途径、肠道微生物群、关键基因靶点及功能途径以及“行为-微生物群-代谢物”关系等方面探讨 JCJ 治疗 AFC 的潜在机制。

方法

采用 16S rRNA 分析和粪便代谢组学结合网络药理学方法，研究 AFC 大鼠的异常表现以及 JCJ 的调节作用。

结果

JCJ 显著调节了 AFC 大鼠行为、微生物丰富度和代谢物图谱的异常。发现 19 种代谢物与 AFC 相关，涉及 15 条代谢途径。令人高兴的是，JCJ 显著调节了 9 种代谢物和 6 条代谢途径。AFC 显著中断了 4 种差异细菌的水平，而 JCJ 显著调节了 SMB53 的水平。HSP90AA1 和 TP53 是关键基因，癌症途径是涉及 JCJ 机制的最相关信号通路。