BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.展开更多
BACKGROUND Irritable bowel syndrome with predominant constipation(IBS-C)is a chronic gastrointestinal disorder that significantly impacts the quality of life of patients and currently lacks a definitive treatment.The ...BACKGROUND Irritable bowel syndrome with predominant constipation(IBS-C)is a chronic gastrointestinal disorder that significantly impacts the quality of life of patients and currently lacks a definitive treatment.The use of electroacupuncture(EA)has demonstrated clinical efficacy in treating IBS-C and the gut-brain axis modulation,though its mechanisms remain unclear.AIM To investigate gut-brain-microbiota axis alteration and EA-associated microbial changes in IBS-C patients and treatment responders.METHODS This study consisted of two phases.The first phase was a cross-sectional study recruiting sixteen IBS-C patients and 16 healthy controls.Baseline fecal samples were collected to assess gut microbiota profiles between the two groups.The second phase was an observational longitudinal study in which the 16 IBS-C patients underwent nine EA sessions over one month.Gut microbiota profiles and clinical outcomes were assessed post-treatment course and at a one-month follow-up.RESULTS IBS-C patients exhibited significant gut dysbiosis,as indicated by altered beta diversity compared to healthy controls.EA significantly improved clinical outcomes and gut dysbiosis,with sustained therapeutic effects and normalization of neurotransmitter-related metabolic pathways observed at one-month follow-up.Notably,the gut bacterium Senegalimassilia was positively associated with symptom improvement,suggesting its potential as a predictive biomarker of EA responsiveness.CONCLUSION These findings support the integration of EA into IBS-C management and highlight Senegalimassilia as a candidate microbial biomarker for treatment response.展开更多
BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to ...BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation.The pathophysiology of functional constipation(FC)is associated with a reduction in mucin-2(MUC2)secretion and microbial dysbiosis.AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota.METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action.FC model was induced via loperamide gavage(16 mg/kg)twice daily for 7 days.Applying defecation function and gastrointestinal motility to assess constipation severity.Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology.Transmission electron microscope was used to observe the ultrastructure of goblet cells(GCs).Immunofluorescence colocalization,quantitative PCR,and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway.16S rDNA was employed to sequence the gut mucosal microbiota.RESULTS RCNSP contained 12 components with potential laxative effects.It enhanced defecation function,accelerated gastrointestinal motility,and maintained colonic mucosal integrity.RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure.At the molecular level,RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway.Through 16S rDNA sequencing analysis,RCNSP significantly altered the mucosal microbiota composition.Specifically,it increased beneficial bacterial strains while reducing harmful ones.Simultaneously,RCNSP reduced butyrate-producing bacteria like Proteobacteria,Enterobacteriaceae,Blautia,and Eubacterium and decreased hydrogen sulfide-producing species,such as Prevotellaceae.It also reduced bile acidinhibiting species,such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acidproducing species,such as Colidextribacter.CONCLUSION Our findings suggested that RCNSP ameliorated constipation through a dual mechanism:It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.展开更多
BACKGROUND Elobixibat reportedly improves bowel movements in patients with chronic constipation.However,its effect on bowel movements in elderly patients with chronic constipation in clinical settings has not been exa...BACKGROUND Elobixibat reportedly improves bowel movements in patients with chronic constipation.However,its effect on bowel movements in elderly patients with chronic constipation in clinical settings has not been examined.AIM To examine bowel movement frequency and stool form before and after elobixibat administration in elderly patients with chronic constipation at our clinic.METHODS A total of 10 mg elobixibat was administered to 35(<65 years old)patients and 45(≥65 years old)patients with chronic constipation.The frequency of bowel movements and stool forms,assessed using the Bristol Stool Form Scale(BSFS),were compared between the two groups 1 week before and after elobixibat administration.RESULTS In patients aged<65 years with chronic constipation,the pre-elobixibat frequency of bowel movements and BSFS scores were 2.167±0.732 and 2.286±0.742,respectively.After elobixibat administration,the frequency of bowel movements and BSFS scores improved to 2.389±0.502 and 3.995±0.566,respectively,showing a significant improvement in bowel movement status.In patients aged≥65 years with chronic constipation,the pre-elobixibat frequency of bowel movements and BSFS scores were 2.003±0.733 and 2.217±0.758,respectively.After elobixibat administration,the frequency of bowel movements and BSFS scores improved to 4.402±1.346 and 3.800±0.704,respectively,indicating an improvement in bowel movement status(P<0.001).No significant differences were observed in the frequency and improvement status of bowel movements or BSFS scores between patients with chronic constipation aged≥65 years and<65 years.Adverse events due to the administration of elobixibat occurred in 16 cases(20%).No significant differences were found in the incidence of adverse events between patients with chronic constipation aged<65 years(8 cases,22.9%)and those aged≥65 years(8 cases,17.8%).CONCLUSION Elobixibat is effective in improving bowel movement status in patients with chronic constipation.No significant differences were found in the improvement of bowel movement status or the incidence of adverse events between patients with chronic constipation aged<65 years and≥65 years,suggesting that the drug may be safely used in elderly patients.展开更多
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
文摘BACKGROUND Irritable bowel syndrome with predominant constipation(IBS-C)is a chronic gastrointestinal disorder that significantly impacts the quality of life of patients and currently lacks a definitive treatment.The use of electroacupuncture(EA)has demonstrated clinical efficacy in treating IBS-C and the gut-brain axis modulation,though its mechanisms remain unclear.AIM To investigate gut-brain-microbiota axis alteration and EA-associated microbial changes in IBS-C patients and treatment responders.METHODS This study consisted of two phases.The first phase was a cross-sectional study recruiting sixteen IBS-C patients and 16 healthy controls.Baseline fecal samples were collected to assess gut microbiota profiles between the two groups.The second phase was an observational longitudinal study in which the 16 IBS-C patients underwent nine EA sessions over one month.Gut microbiota profiles and clinical outcomes were assessed post-treatment course and at a one-month follow-up.RESULTS IBS-C patients exhibited significant gut dysbiosis,as indicated by altered beta diversity compared to healthy controls.EA significantly improved clinical outcomes and gut dysbiosis,with sustained therapeutic effects and normalization of neurotransmitter-related metabolic pathways observed at one-month follow-up.Notably,the gut bacterium Senegalimassilia was positively associated with symptom improvement,suggesting its potential as a predictive biomarker of EA responsiveness.CONCLUSION These findings support the integration of EA into IBS-C management and highlight Senegalimassilia as a candidate microbial biomarker for treatment response.
基金Supported by National Natural Science Foundation of China,No.82174309and Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Siming Fund Special Project for Scientific Research,No.SGKJ-202304.
文摘BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation.The pathophysiology of functional constipation(FC)is associated with a reduction in mucin-2(MUC2)secretion and microbial dysbiosis.AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota.METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action.FC model was induced via loperamide gavage(16 mg/kg)twice daily for 7 days.Applying defecation function and gastrointestinal motility to assess constipation severity.Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology.Transmission electron microscope was used to observe the ultrastructure of goblet cells(GCs).Immunofluorescence colocalization,quantitative PCR,and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway.16S rDNA was employed to sequence the gut mucosal microbiota.RESULTS RCNSP contained 12 components with potential laxative effects.It enhanced defecation function,accelerated gastrointestinal motility,and maintained colonic mucosal integrity.RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure.At the molecular level,RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway.Through 16S rDNA sequencing analysis,RCNSP significantly altered the mucosal microbiota composition.Specifically,it increased beneficial bacterial strains while reducing harmful ones.Simultaneously,RCNSP reduced butyrate-producing bacteria like Proteobacteria,Enterobacteriaceae,Blautia,and Eubacterium and decreased hydrogen sulfide-producing species,such as Prevotellaceae.It also reduced bile acidinhibiting species,such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acidproducing species,such as Colidextribacter.CONCLUSION Our findings suggested that RCNSP ameliorated constipation through a dual mechanism:It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.
文摘BACKGROUND Elobixibat reportedly improves bowel movements in patients with chronic constipation.However,its effect on bowel movements in elderly patients with chronic constipation in clinical settings has not been examined.AIM To examine bowel movement frequency and stool form before and after elobixibat administration in elderly patients with chronic constipation at our clinic.METHODS A total of 10 mg elobixibat was administered to 35(<65 years old)patients and 45(≥65 years old)patients with chronic constipation.The frequency of bowel movements and stool forms,assessed using the Bristol Stool Form Scale(BSFS),were compared between the two groups 1 week before and after elobixibat administration.RESULTS In patients aged<65 years with chronic constipation,the pre-elobixibat frequency of bowel movements and BSFS scores were 2.167±0.732 and 2.286±0.742,respectively.After elobixibat administration,the frequency of bowel movements and BSFS scores improved to 2.389±0.502 and 3.995±0.566,respectively,showing a significant improvement in bowel movement status.In patients aged≥65 years with chronic constipation,the pre-elobixibat frequency of bowel movements and BSFS scores were 2.003±0.733 and 2.217±0.758,respectively.After elobixibat administration,the frequency of bowel movements and BSFS scores improved to 4.402±1.346 and 3.800±0.704,respectively,indicating an improvement in bowel movement status(P<0.001).No significant differences were observed in the frequency and improvement status of bowel movements or BSFS scores between patients with chronic constipation aged≥65 years and<65 years.Adverse events due to the administration of elobixibat occurred in 16 cases(20%).No significant differences were found in the incidence of adverse events between patients with chronic constipation aged<65 years(8 cases,22.9%)and those aged≥65 years(8 cases,17.8%).CONCLUSION Elobixibat is effective in improving bowel movement status in patients with chronic constipation.No significant differences were found in the improvement of bowel movement status or the incidence of adverse events between patients with chronic constipation aged<65 years and≥65 years,suggesting that the drug may be safely used in elderly patients.
