Shouhui Tongbian Capsule ameliorates constipation via gut microbiota-5-HT-intestinal motility axis

被引:37
作者
Bai, Jinzhao [1 ]
Cai, Yajie [1 ]
Huang, Zhiyan [2 ]
Gu, Yiqing [1 ]
Huang, Nana [4 ]
Sun, Rong [4 ,5 ]
Zhang, Guimin [2 ,3 ,6 ]
Liu, Runping [1 ,7 ]
机构
[1] Beijing Univ Chinese Med, Sch Mat Med, Beijing 100029, Peoples R China
[2] Lunan Hope Pharmaceut Co Ltd, Linyi 276006, Peoples R China
[3] Lunan Pharmaceut Grp Co Ltd, State Key Lab Gener Manufacture Technol Chinese Tr, Linyi 276006, Peoples R China
[4] Shandong Univ, Hosp 2, Jinan 250033, Peoples R China
[5] Shandong Univ, Hosp 2, 247 Beiyuandajie, Jinan 250003, Peoples R China
[6] Lunan Hope Pharmaceut Co Ltd, 209 Hongqi Rd, Linyi 276006, Peoples R China
[7] Beijing Univ Chinese Med, Sch Chinese Mat Med, 11 Bei San Huan Dong Rd, Beijing 100029, Peoples R China
基金
中国国家自然科学基金;
关键词
Shouhui Tongbian Capsules; Gut microbiota; 5-HT; Enteric nervous system; Gastrointestinal motility; FECAL MICROBIOTA TRANSPLANTATION; CHAIN FATTY-ACIDS; SEROTONIN; RECEPTOR;
D O I
10.1016/j.biopha.2022.113627
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Constipation has become an epidemic enteric medical problem, accompanied with increasing long-term sequelae. Gut microbiota and serotonin (5-HT) have been believed as predominant player in the treatment of constipation. In clinical practices, Shouhui Tongbian Capsule (SHTB) was found to effectively improve constipation symptoms and promote gastrointestinal motility. However, the specific mechanism of SHTB is not clearly elucidated. Our current study aims to explore the therapeutic effects of SHTB against the development of constipation and the underlying mechanisms related to gut bacterial and 5-HT. We established loperamide hydrochloride (LH)-induced experimental constipation mouse model to evaluate the effect of SHTB. 16S RNA sequencing, fecal microbiota transplants (FMT), high performance liquid chromatograph, and molecular biological analysis were performed to investigate the potential mechanisms of SHTB. Our data demonstrated that SHTB significantly ameliorated LH-induced experimental constipation and accelerated enteric motility via promoting 5-HT biosynthesis in enterochromaffin cells and enteric neuron growth of the enteric nervous system (ENS) in both the small intestine and colon. Additionally, SHTB significantly modulated gut microbiota dysbiosis and potentially altered microbiota metabolites to enhance intestinal 5-HT production. Finally, FMT study confirmed that the effects of SHTB on 5-HT production and constipation are dependent on modulating intestinal microbiota dysbiosis. In conclusion, our current study deciphered therapeutic mechanism of SHTB in the treatment of experimental constipation from perspectives of gut microbiota-5-HT-intetinal motility axis and provides novel insights into the appropriate and safe application of SHTB in the clinic.
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页数:16
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