OBJECTIVE:To investigate the effect of slow transit constipation(STC)and spleen Qi deficiency on gut microbiota,and the mechanism underlying the action that the positive drug Maren Runchang(MR)alleviates STC.METHODS:S...OBJECTIVE:To investigate the effect of slow transit constipation(STC)and spleen Qi deficiency on gut microbiota,and the mechanism underlying the action that the positive drug Maren Runchang(MR)alleviates STC.METHODS:STC was induced,using the cathartic method of Senna and the hunger-fullness disorder method,in ICR mice;one group of model mice was treated with MR(6.24 g/kg).The changes in the general condition,fecal parameters,D-xylose content in the serum,intestinal propulsion rate,and histopathology of the colon were assessed after STC induction in the control,model,and MR groups.Fecal microbiota transplantation(FMT)was performed from STC mice into pseudo germ-free mice.Changes in the contents of substance P(SP),vasoactive intestinal peptide(VIP),and gut microbiota in STC mice and pseudo germ-free mice were assessed after FMT.RESULTS:Compared with the control group,the model mice showed the following results:the time of the first black stool was significantly longer(P<0.01),the number and weight of black stools were significantly reduced within 6 h(P<0.05),the D-xylose content in the serum was significantly reduced(P<0.05),the intestinal propulsion rate decreased(P<0.01),the content of VIP in colon tissue significantly increased(P<0.05),and SP content in the colon tissue significantly decreased(P<0.01);moreover,the colon showed significant inflamemation and injury.Furthermore,the abundance of Firmicutes was increased,the abundance of Bacteroides decreased,and the abundance of Alistipes,unclassified_o_Bacteroidales,Alloprevotella,Bilophila,and Anaerotruncus decreased,while the abundance of the conditional pathogenic bacteria Escherichia and Klebsiella increased.However,after treatment with MR,the time of the first black stool decreased(P<0.01),the number of black stools within 6 h increased,and the intestinal propulsion rate increased(P<0.05).Moreover,the content of D-xylose in the serum and the content of VIP in colon tissue significantly decreased(P<0.05),the content of SP in colon tissue significantly increased(P<0.01),and colon inflammation significantly improved.Additionally,the abundance of Firmicutes decreased,and the abundance of Bacteroides increased.The abundance of unclassified_o_Bacteroidales and Bilophila increased,and the abundance of Klebsiella decreased.In the model+FMT group,compared with control+FMT group,the content of VIP in colon tissue decreased(P<0.05),the content of SP in colon tissue significantly increased(P<0.01),and the abundance of probiotics,such as Lactobacillus and Akkermansia,decreased.In the MR+FMT group,compared with the model+FMT group,the content of VIP in colon tissue increased,the content of SP in colon tissue significantly decreased(P<0.01),and the abundance of probiotics increased.CONCLUSIONS:STC mice with spleen Qi deficiency show a decreased abundance of beneficial bacteria,such as Alistipes,unclassified_o_Bacteroidales,Alloprevotella,Bilophila,and Anaerotruncus,and an increased abundance of the conditional pathogenic bacteria Escherichia coli and Klebsiella.Furthermore,the mechanism of action of MR in treating STC may involve the regulation of intestinal movement,reduction of intestinal inflammation,elevation of intestinal absorption,and regulation of gut microbiota.展开更多
基金Supported by Fundamental Scientific Research Business Fees of Central Public Welfare Scientific Research Institutes of China Academy of Chinese Medical Sciences(No.Z2021022)National Natural Science(No.81891010):Study on the Authenticity of Traditional Chinese Medicine,Science and Technology Innovation Project of China Academy of Chinese Medical Sciences:Efficacy Evaluation and Mechanism Exploration of Huashi Baidu Granule based on"multi-link and multi-target"in the Prevention and Treatment of Influenza Virus Infection(CI2021A04605)Basic Scientific Research Business Fee Project of Central Public Welfare Scientific Research Institutes of the Chinese Academy of Chinese Medical Sciences:Study on the Novel Coronavirus Pneumonia Mechanism of Yiqi Zeng Fang and Huashi Baidu Granules(ZZ15-WT-04)
文摘OBJECTIVE:To investigate the effect of slow transit constipation(STC)and spleen Qi deficiency on gut microbiota,and the mechanism underlying the action that the positive drug Maren Runchang(MR)alleviates STC.METHODS:STC was induced,using the cathartic method of Senna and the hunger-fullness disorder method,in ICR mice;one group of model mice was treated with MR(6.24 g/kg).The changes in the general condition,fecal parameters,D-xylose content in the serum,intestinal propulsion rate,and histopathology of the colon were assessed after STC induction in the control,model,and MR groups.Fecal microbiota transplantation(FMT)was performed from STC mice into pseudo germ-free mice.Changes in the contents of substance P(SP),vasoactive intestinal peptide(VIP),and gut microbiota in STC mice and pseudo germ-free mice were assessed after FMT.RESULTS:Compared with the control group,the model mice showed the following results:the time of the first black stool was significantly longer(P<0.01),the number and weight of black stools were significantly reduced within 6 h(P<0.05),the D-xylose content in the serum was significantly reduced(P<0.05),the intestinal propulsion rate decreased(P<0.01),the content of VIP in colon tissue significantly increased(P<0.05),and SP content in the colon tissue significantly decreased(P<0.01);moreover,the colon showed significant inflamemation and injury.Furthermore,the abundance of Firmicutes was increased,the abundance of Bacteroides decreased,and the abundance of Alistipes,unclassified_o_Bacteroidales,Alloprevotella,Bilophila,and Anaerotruncus decreased,while the abundance of the conditional pathogenic bacteria Escherichia and Klebsiella increased.However,after treatment with MR,the time of the first black stool decreased(P<0.01),the number of black stools within 6 h increased,and the intestinal propulsion rate increased(P<0.05).Moreover,the content of D-xylose in the serum and the content of VIP in colon tissue significantly decreased(P<0.05),the content of SP in colon tissue significantly increased(P<0.01),and colon inflammation significantly improved.Additionally,the abundance of Firmicutes decreased,and the abundance of Bacteroides increased.The abundance of unclassified_o_Bacteroidales and Bilophila increased,and the abundance of Klebsiella decreased.In the model+FMT group,compared with control+FMT group,the content of VIP in colon tissue decreased(P<0.05),the content of SP in colon tissue significantly increased(P<0.01),and the abundance of probiotics,such as Lactobacillus and Akkermansia,decreased.In the MR+FMT group,compared with the model+FMT group,the content of VIP in colon tissue increased,the content of SP in colon tissue significantly decreased(P<0.01),and the abundance of probiotics increased.CONCLUSIONS:STC mice with spleen Qi deficiency show a decreased abundance of beneficial bacteria,such as Alistipes,unclassified_o_Bacteroidales,Alloprevotella,Bilophila,and Anaerotruncus,and an increased abundance of the conditional pathogenic bacteria Escherichia coli and Klebsiella.Furthermore,the mechanism of action of MR in treating STC may involve the regulation of intestinal movement,reduction of intestinal inflammation,elevation of intestinal absorption,and regulation of gut microbiota.