Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China.
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Taiyuan 030006, China.
J Proteome Res. 2021 Oct 1;20(10):4771-4786. doi: 10.1021/acs.jproteome.1c00435. Epub 2021 Sep 15.
Constipation and depression are tightly related and often co-occur and coexist in clinic. Yet, the relationships and the underlying mechanisms are still unclear. Fecal metabolomics and network pharmacology were, for the first time, applied to investigate the potential correlations from multiple levels including classic behaviors, metabolomics, and gene targets. The behavioral indicators were analyzed, providing behavioral correlations at a macrolevel. Besides, fecal samples were analyzed by nuclear magnetic resonance spectroscopy to screen the shared and the unique metabolites and pathways, revealing correlations from a metabolic perspective. Finally, the disease targets and the functional pathways were obtained via network pharmacology, demonstrating correlations at the molecular level. The correlations between constipation and depression were demonstrated and supported by four-level evidence: (1) general behaviors, (2) gastrointestinal functions, (3) fecal metabolites and pathways, and (4) common gene targets and functional pathways. Especially, the correlations of behaviors and common metabolites showed that metabolites, including choline, betaine, and glycine, were significantly associated with constipation and depression. Besides, inflammation and immune abnormalities and energy metabolism were significantly involved in the mechanisms. The current findings prove the correlations between constipation and depression, and provide a basis for deeply understanding the comorbidities of constipation and depression.
便秘和抑郁密切相关，在临床上常同时发生和共存。然而，它们之间的关系和潜在机制仍不清楚。本研究首次将粪便代谢组学和网络药理学应用于从经典行为、代谢组学和基因靶点等多个层面来探讨潜在的相关性。分析了行为学指标，提供了宏观水平的行为相关性。此外，还通过核磁共振波谱法分析粪便样本，以筛选共享和独特的代谢物和途径，从代谢角度揭示相关性。最后，通过网络药理学获得疾病靶点和功能途径，从分子水平上证明相关性。便秘和抑郁之间的相关性通过四级证据得到了证实和支持：（1）一般行为；（2）胃肠道功能；（3）粪便代谢物和途径；（4）共同的基因靶点和功能途径。特别是，行为和共同代谢物的相关性表明，包括胆碱、甜菜碱和甘氨酸在内的代谢物与便秘和抑郁显著相关。此外，炎症和免疫异常以及能量代谢也显著参与其中。本研究结果证明了便秘和抑郁之间的相关性，为深入了解便秘和抑郁的共病提供了依据。
