慢传输型便秘（STC）的发生与肠道Cajal间质细胞（ICC）减少、菌群及微环境异常相关，但机制尚不清楚。我们已证实STC患者肠道ICC数量及乳酸/双歧杆菌显著减少；且乳酸和乙酸代谢减少；黄芪汤可显著改善STC症状。已知黄芪可改善肠道益生菌群。因此我们提出：黄芪汤是否可改善局部酸性微环境，提高ICC数量进而缓解STC的发生？进一步的预实验发现：黄芪汤的关键单体黄芪甲苷可提高罗伊氏乳杆菌的菌群数量，并促进其分泌乳酸；乳酸可结合ICC胞膜受体GPR81，激活Wnt3通路分子；黄芪甲苷可增加ICC数量。已知Wnt3是促进细胞增殖的关键通路分子！基于此，我们提出黄芪甲苷改善STC的“菌群-微环境-细胞”新通路：黄芪甲苷促进罗伊氏乳杆菌分泌乳酸，结合于ICC的GPR81，激活Wnt3通路，启动下游分子促进ICC增殖来改善STC。本项目拟运用宏基因组测序等技术阐明上述机制，为STC治疗提供理论基础。

The occurrence of slow transit constipation (STC) is closely related to the reduction of interstitial cells of Cajal (ICC), microflora and microenvironment abnormalities in the intestines, but the underlying mechanism is still unclear. We have confirmed that the number of ICC and lactic acid/Bifidobacteria in the intestinal tract of STC patients are significantly reduced; and the metabolism of lactic acid and acetic acid decreased. Besides, Huangqi decoction significantly alleviates the symptoms of STC. It is known that Huangqi can improve the secretion of intestinal probiotic flora. Therefore, the results suggest that Huangqi Tang can improve the local acid microenvironment, increase the number of ICC, and finally alleviate the symptoms of STC. Further experiments found that the key monomer of Huangqi decoction, astragaloside IV, can increase the number of microflora in Lactobacillus reuteri and promote its secretion of lactic acid, lactic acid can bind to ICC cell membrane receptor GPR81 and activate the Wnt3 pathway. Moreover, astragaloside IV can increase the number of ICCs. As Wnt3 is known to be a key pathway molecule that promotes cell proliferation, we suppose that astragaloside IV can treat STC depending on the new pathway of "microflora-microenvironment-cell". Astragaloside IV promotes the secretion of lactic acid by Lactobacillus reuteri, which binds to GPR81 of ICC, activates the Wnt3 pathway, and initiates downstream molecules to promote the proliferation of ICC in STC. This research intends to use the technology of metagenomic sequencing to clarify the above molecular mechanism, and provide a theoretical basis for the treatment of STC. Therefore, this project has important theoretical and clinical value.