[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae)...[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.展开更多
BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activit...BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.展开更多
Background:Fecal microbiota transplantation(FMT)based on the positive ion mode of metabonomics has a good therapeutic benefit for slow transit constipation(STC)patients.However,a piece of comprehensive metabolomics in...Background:Fecal microbiota transplantation(FMT)based on the positive ion mode of metabonomics has a good therapeutic benefit for slow transit constipation(STC)patients.However,a piece of comprehensive metabolomics information is yet to be established.The aim of the study was to explore the efficacy and mechanism of FMT in the treatment of STC under metabonomics.Methods:Eight STC patients meeting the set inclusion and exclusion criteria were enrolled and treated with FMT(three times).The Patient Assessment of Constipation-Symptoms(PAC-SYM),weekly total defecation times,and defecation frequency scores of these STC patients were compared before and after treatment.Feces and serum of STC patients before and after treatment were analyzed using 16SrDNA and metabolomics.Results:After FMT treatment,the PAC-SYM score of constipated patients decreased[(5.00±2.94)vs(5.20±2.87)],while the number of complete defecations per week increased[(2.00±1.79)vs(1.69±1.80)].The score of defecation frequency decreased[(0.83±1.03)vs(0.86±0.95)].The metabolites in the feces and serum of patients receiving FMT changed significantly(P<0.05).The results from 16SrDNA analysis showed that theαandβdiversity of the fecal microbiome changed significantly(P<0.05)after transplantation,and the contents of genera Lactobacillus,Bacillus,Succiniclasticum,Cellvibrio,and Escherichia increased in FMT treated patients.Conclusion:FMT may treat STC by increasing the beneficial intestinal flora and metabolites in the anion mode of metabolomics.展开更多
Slow transit constipation(STC),one of the most common chronic constipation in the clinic,is characterized by prolonged colonic transit time.Pathogenesis is unclear,and abnormalities can be found in enteric nervous sys...Slow transit constipation(STC),one of the most common chronic constipation in the clinic,is characterized by prolonged colonic transit time.Pathogenesis is unclear,and abnormalities can be found in enteric nervous system,intestinal neurotransmitters,intestinal smooth muscle,and Cajal stromal cell.Various methods have been used to improve the quality of life of patients with STC,including dietary fiber supplements,various cathartics,prokinetic drugs,and surgical intervention.However,there are still a large number of patients showing poor response to conservative treatment and intolerance to surgical treatment.Patients with STC suffer from severe constipation for long periods of time,faced with heavy economic burden and mental torture.Exploration the pathogenesis of STC to provide a clearer direction for future drug development is needed.展开更多
BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipati...BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation,leading to an abnormal distribution and dysfunction of ICC in the diseased colon,which promotes the occurrence and development of STC.展开更多
BACKGROUND Slow transit constipation(STC)has traditionally been considered as a functional disorder.However,evidence is accumulating that suggests that most of the motility alterations in STC might be of a neuropathic...BACKGROUND Slow transit constipation(STC)has traditionally been considered as a functional disorder.However,evidence is accumulating that suggests that most of the motility alterations in STC might be of a neuropathic etiology.If the patient does not meet the diagnosis of pelvic outlet obstruction and poorly response to conservative treatment,surgical intervention with subtotal colectomy may be effective.The most unwanted complication of the procedure is anastomotic leakage,however,preservation of the superior rectal artery(SRA)may reduce its incidence.AIM To evaluate the preservation of the SRA in laparoscopically assisted subtotal colectomy with ileorectal anastomosis in STC patients.METHODS This was a single-center retrospective observational study.STC was diagnosed after a series of examinations which included a colonic transit test,anal manometry,a balloon expulsion test,and a barium enema.Eligible patients underwent laparoscopically assisted total colectomy with ileorectal anastomosis and were examined between January 2016 and January 2018.The operation time,blood loss,time to first flatus,length of hospital days,and incidence of minor or major complications were recorded.RESULTS A total of 32 patients(mean age,42.6 years)who had received laparoscopic assisted subtotal colectomy with ileorectal artery anastomosis and preservation of the SRA.All patients were diagnosed with STC after a series of examinations.The mean operative time was 151 min and the mean blood loss was 119 mL.The mean day of first time to flatus was 3.0 d,and the mean hospital stay was 10.6 d.There were no any patients conversions to laparotomy.Post-operative minor complications including 1 wound infection and 1 case of ileus.There was no surgical mortality.No anastomosis leakage was noted in any of the patients.CONCLUSION Laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the SRA can significantly improve bowel function with careful patient selection.Sparing the SRA may protect against anastomosis leakage.展开更多
Objective:To explore the possible effects and mechanism of Zhizhu Decoction(ZZD)on the pathophysiology of slow transit constipation(STC).Methods A total of 54 C57BL/6 mice was randomly divided into the following 6 gro...Objective:To explore the possible effects and mechanism of Zhizhu Decoction(ZZD)on the pathophysiology of slow transit constipation(STC).Methods A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table,including control,STC model(model),positive control,and low-,medium-and high-doses ZZD treatment groups(5,10,20 g/kg,namely L,M-,and H-ZZD,respectively),9 mice in each group.Following 2-week treatment,intestinal transport rate(ITR)and fecal water content were determined,and blood and colon tissue samples were collected.Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells.To determine intestinal permeability,serum levels of lipopolysaccharide(LPS),low-density lipoprotein(LDL)and mannose were measured using enzyme-linked immunosorbent assay(ELISA).Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1(ZO-1),claudin-1,occludin and recombinant mucin 2(MUC2).The mRNA expression levels of inflammatory cytokines including tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,IL-4,IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction.Colon indexes of oxidative stress were measured by ELISA,and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1(SIRT1/FoxO1)antioxidant signaling pathway were detected by Western blot.Results Compared with the model group,ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups(P<0.01).Additionally,ZZD treatment notably increased the thickness of mucosal and muscular tissue,elevated the number of goblet cells in the colon of STC mice,reduced the secretion levels of LPS,LDL and mannose,and upregulated ZO-1,claudin-1,occludin and MUC2 expressions in the colon in a dose-dependent manner,compared with the model group(P<0.05 or P<0.01).In addition,ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway(P<0.05 or P<0.01).Conclusion ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.展开更多
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
Objective To investigate motor activity of gastrointestinal tract in patients with slow transit constipation. Methods 42 patients with STC and 20 healthy controls were included in the study. Each subject underwent col...Objective To investigate motor activity of gastrointestinal tract in patients with slow transit constipation. Methods 42 patients with STC and 20 healthy controls were included in the study. Each subject underwent colonic transit test, gastric emptying, orocecal transit time, electromyography and anorectal manometry. Results According to transit index, 42 STC patients were divided into 3 types: ①0.5<TI≤1.0, slow rectosigmoid transit 15 cases; ②TI=0.5, colorectal stasis 10 cases; ③0<TI≤0.5, slow colonic transit 17 cases. Gastric emptying rate at the fourth hour was decreased in STC patients than in controls . The mean orocaecal transit time was significantly delayed in the patients . Paradoxical anal sphincter contraction with defecation effort was higher prevalent in patients with slow rectosigmoid transit and colorectal stasis than patients with slow colonic transit. Minimum relaxation volume and maximal rectal tolerable volume were significantly increased in STC patients . Conclusion STC displayed colonic abnormality, and/or pelvic floor dysfunction. In addition, it showed motor abnormalities of upper gut, might be part of a pan enteric motor disorders.展开更多
基金Supported by The Natural Science Foundation of Guizhou Province (Qiankehe Jichu[2020]1Y362)Special Project for Scientific and Technological Research on Traditional Chinese Medicine and Ethnic Medicine of Guizhou Province(QZYY-2021-016)+1 种基金The Natural Science Foundation of Guizhou Province(Qiankehe Jichu-ZK[2022]Yiban 510)Young Science and Technology Talents Growth Project of Guizhou Provincial Department of Education (Qian Jiao He KY Zi[2022]No. 261)。
文摘[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.
基金Supported by the "333 Scientific Project" of Jiangsu Province in 2020, No. BRA2020237the Science and Technology Project of Suqian, Jiangsu Province in 2020, No. Z2020057
文摘BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.
基金National Key R&D Program of China(No.2018YFC1706506)Foundation of Tianjin Municipal Health Commission(No.ZC20097)+2 种基金Foundation of Tianjin Union Medical Center(No.2020YJ017,2017YJZD005)National Natural Science Foundation of China(No.82174374)College of Integrated Traditional Chinese and Western Medicine,Tianjin University of Traditional Chinese Medicine 2021 Postgraduate Innovation Fund(No.ZXYCXLX202115).
文摘Background:Fecal microbiota transplantation(FMT)based on the positive ion mode of metabonomics has a good therapeutic benefit for slow transit constipation(STC)patients.However,a piece of comprehensive metabolomics information is yet to be established.The aim of the study was to explore the efficacy and mechanism of FMT in the treatment of STC under metabonomics.Methods:Eight STC patients meeting the set inclusion and exclusion criteria were enrolled and treated with FMT(three times).The Patient Assessment of Constipation-Symptoms(PAC-SYM),weekly total defecation times,and defecation frequency scores of these STC patients were compared before and after treatment.Feces and serum of STC patients before and after treatment were analyzed using 16SrDNA and metabolomics.Results:After FMT treatment,the PAC-SYM score of constipated patients decreased[(5.00±2.94)vs(5.20±2.87)],while the number of complete defecations per week increased[(2.00±1.79)vs(1.69±1.80)].The score of defecation frequency decreased[(0.83±1.03)vs(0.86±0.95)].The metabolites in the feces and serum of patients receiving FMT changed significantly(P<0.05).The results from 16SrDNA analysis showed that theαandβdiversity of the fecal microbiome changed significantly(P<0.05)after transplantation,and the contents of genera Lactobacillus,Bacillus,Succiniclasticum,Cellvibrio,and Escherichia increased in FMT treated patients.Conclusion:FMT may treat STC by increasing the beneficial intestinal flora and metabolites in the anion mode of metabolomics.
文摘Slow transit constipation(STC),one of the most common chronic constipation in the clinic,is characterized by prolonged colonic transit time.Pathogenesis is unclear,and abnormalities can be found in enteric nervous system,intestinal neurotransmitters,intestinal smooth muscle,and Cajal stromal cell.Various methods have been used to improve the quality of life of patients with STC,including dietary fiber supplements,various cathartics,prokinetic drugs,and surgical intervention.However,there are still a large number of patients showing poor response to conservative treatment and intolerance to surgical treatment.Patients with STC suffer from severe constipation for long periods of time,faced with heavy economic burden and mental torture.Exploration the pathogenesis of STC to provide a clearer direction for future drug development is needed.
文摘BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation,leading to an abnormal distribution and dysfunction of ICC in the diseased colon,which promotes the occurrence and development of STC.
基金This study protocol was reviewed and approved by the Institutional Review Board of the Taiwan Adventist Hospital(TAHIRB No.:105-E-10).
文摘BACKGROUND Slow transit constipation(STC)has traditionally been considered as a functional disorder.However,evidence is accumulating that suggests that most of the motility alterations in STC might be of a neuropathic etiology.If the patient does not meet the diagnosis of pelvic outlet obstruction and poorly response to conservative treatment,surgical intervention with subtotal colectomy may be effective.The most unwanted complication of the procedure is anastomotic leakage,however,preservation of the superior rectal artery(SRA)may reduce its incidence.AIM To evaluate the preservation of the SRA in laparoscopically assisted subtotal colectomy with ileorectal anastomosis in STC patients.METHODS This was a single-center retrospective observational study.STC was diagnosed after a series of examinations which included a colonic transit test,anal manometry,a balloon expulsion test,and a barium enema.Eligible patients underwent laparoscopically assisted total colectomy with ileorectal anastomosis and were examined between January 2016 and January 2018.The operation time,blood loss,time to first flatus,length of hospital days,and incidence of minor or major complications were recorded.RESULTS A total of 32 patients(mean age,42.6 years)who had received laparoscopic assisted subtotal colectomy with ileorectal artery anastomosis and preservation of the SRA.All patients were diagnosed with STC after a series of examinations.The mean operative time was 151 min and the mean blood loss was 119 mL.The mean day of first time to flatus was 3.0 d,and the mean hospital stay was 10.6 d.There were no any patients conversions to laparotomy.Post-operative minor complications including 1 wound infection and 1 case of ileus.There was no surgical mortality.No anastomosis leakage was noted in any of the patients.CONCLUSION Laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the SRA can significantly improve bowel function with careful patient selection.Sparing the SRA may protect against anastomosis leakage.
基金Supported by the General Project of National Natural Science Foundation of China(No.82074429)。
文摘Objective:To explore the possible effects and mechanism of Zhizhu Decoction(ZZD)on the pathophysiology of slow transit constipation(STC).Methods A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table,including control,STC model(model),positive control,and low-,medium-and high-doses ZZD treatment groups(5,10,20 g/kg,namely L,M-,and H-ZZD,respectively),9 mice in each group.Following 2-week treatment,intestinal transport rate(ITR)and fecal water content were determined,and blood and colon tissue samples were collected.Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells.To determine intestinal permeability,serum levels of lipopolysaccharide(LPS),low-density lipoprotein(LDL)and mannose were measured using enzyme-linked immunosorbent assay(ELISA).Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1(ZO-1),claudin-1,occludin and recombinant mucin 2(MUC2).The mRNA expression levels of inflammatory cytokines including tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,IL-4,IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction.Colon indexes of oxidative stress were measured by ELISA,and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1(SIRT1/FoxO1)antioxidant signaling pathway were detected by Western blot.Results Compared with the model group,ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups(P<0.01).Additionally,ZZD treatment notably increased the thickness of mucosal and muscular tissue,elevated the number of goblet cells in the colon of STC mice,reduced the secretion levels of LPS,LDL and mannose,and upregulated ZO-1,claudin-1,occludin and MUC2 expressions in the colon in a dose-dependent manner,compared with the model group(P<0.05 or P<0.01).In addition,ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway(P<0.05 or P<0.01).Conclusion ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.
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.
文摘Objective To investigate motor activity of gastrointestinal tract in patients with slow transit constipation. Methods 42 patients with STC and 20 healthy controls were included in the study. Each subject underwent colonic transit test, gastric emptying, orocecal transit time, electromyography and anorectal manometry. Results According to transit index, 42 STC patients were divided into 3 types: ①0.5<TI≤1.0, slow rectosigmoid transit 15 cases; ②TI=0.5, colorectal stasis 10 cases; ③0<TI≤0.5, slow colonic transit 17 cases. Gastric emptying rate at the fourth hour was decreased in STC patients than in controls . The mean orocaecal transit time was significantly delayed in the patients . Paradoxical anal sphincter contraction with defecation effort was higher prevalent in patients with slow rectosigmoid transit and colorectal stasis than patients with slow colonic transit. Minimum relaxation volume and maximal rectal tolerable volume were significantly increased in STC patients . Conclusion STC displayed colonic abnormality, and/or pelvic floor dysfunction. In addition, it showed motor abnormalities of upper gut, might be part of a pan enteric motor disorders.
