Constipation and colonoscopy

Constipation is a significant sociomedical problem,which can be caused by various reasons.In the diagnostic approach to patients with constipation,the following data are usually sufficient:History,complete physical examination(including rectal examination),and additional diagnostic tests.A colonoscopy is not a necessary diagnostic method for all patients with constipation.However,if patients have alarm symptoms/signs,that suggest an organic reason for constipation,a colonoscopy is necessary.The most important alarm symptoms/signs are age>50 years,gastrointestinal bleeding,new-onset constipation,a palpable mass in the abdomen and rectum,weight loss,anemia,inflammatory bowel disease,and family history positive for colorectal cancer.Most endoscopists do not like to deal with patients with constipation.There are two reasons for this,namely the difficulty of endoscopy and the adequacy of preparation.Both are adversely affected by constipation.To improve the quality of colonoscopy in these patients,good examination techniques and often more extensive preparation are necessary.Good colonoscopy technique implies adequate psychological preparation of the patient,careful insertion of the endoscope with minimal insufflation,and early detection and resolution of loops.Bowel preparation for colonoscopy often requires prolonged preparation and sometimes the addition of other laxatives.

Relationship among Parkinson’s disease, constipation, microbes, and microbiological therapy

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson’s disease(PD),a prevalent non-motor symptom contributing significantly to patients’morbidity.A marked alteration in the gut microbiota,predominantly an increase in the abundance of Proteobacteria and Bacteroidetes,is observed in PD-related constipation.Conventional treatments,although safe,have failed to effectively alleviate symptoms,thereby necessitating the development of novel therapeutic strategies.Microbiological interventions such as prebiotics,probiotics,and fecal microbiota transplantation(FMT)hold therapeutic potential.While prebiotics improve bowel movements,probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort.FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD.Despite promising developments,the causal relationship between changes in gut microbiota and PD-related constipation remains elusive,highlighting the need for further research in this expanding field.

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway

BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway.This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats.The serum metabolites,β-leucine(β-Leu)and traumatic acid,were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway,modulating gut microbiota and serum metabolites.β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Preventive effect of kiwi berry(Actinidia arguta)on loperamide-induced constipation

Constipation is a common intestinal disease.Kiwi berries can effectively prevent constipation.However,studies have yet to be done to determine how kiwi berries prevent constipation.For two weeks,mice in this study were continually orally gavaged with kiwi berry,loperamide,or a combination of the 2.This study found that the kiwi group's feces had more water than the constipated mice.In addition,kiwi berries can speed up gastrointestinal transit(GI),shorten the time it takes to pass the first dark stool,and dramatically enhance body weight gain.In the interstitial cells of Caj al(ICC)cells and colon tissues,alterations in the protein expression of vasoactive intestinal peptide(VIP),cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and aquapcrin-3(AQP3)were found.At 3,6,and 12 h of ICC cells and mouse colon,the kiwi group's VIP,cAMP,PKA,and AQP3 protein expression levels were lower than those of the constipated mice.The kiwi berry can decrease the Firmicutes to Bacteroidetes ratio and boost the diversity and quantity of gut microbiota.By influencing the gut microbiota and VIP-cAMP-PKA-AQP3 signaling pathway,kiwi berries prevent constipation.

Assessment of the triglyceride glucose index in adult patients with chronic diarrhea and constipation

BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been investigated.AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation.METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010.TyG was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was performed.The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and constipation.Subgroup analyses were performed to examine the stability of any potential associations.RESULTS In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic constipation.The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations.CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.

Microbiota treatment of functional constipation:Current status and future prospects

Functional constipation(FC)is a common disorder that is characterized by diffi-cult stool passage,infrequent bowel movement,or both.FC is highly prevalent,recurs often,accompanies severe diseases,and affects quality of life;therefore,safe and effective therapy with long-term benefits is urgently needed.Microbiota treatment has potential value for FC treatment.Microbiota treatments include modulators such as probiotics,prebiotics,synbiotics,postbiotics,and fecal micro-biota transplantation(FMT).Some probiotics and prebiotics have been adopted,and the efficacy of other microbiota modulators is being explored.FMT is con-sidered an emerging field because of its curative effects;nevertheless,substantial work must be performed before clinical implementation.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome:A study from China

BACKGROUND Functional constipation(FC)and constipation-predominant irritable bowel syndrome(IBS-C)represent a spectrum of constipation disorders.However,the majority of previous clinical investigations have focused on Western populations,with limited data originating from China.AIM To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population.METHODS Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled.FC and IBS-C diagnoses were established using ROME IV criteria,and patients underwent high-resolution anorectal manometry(ARM)and a colonic transmit test using the Sitz marker study.Constipation-related symptoms were obtained through questionnaires.Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21.The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared.RESULTS No significant differences in sex,age or abdominal discomfort symptoms were observed between IBS-C and FC patients(all P>0.05).The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC(36.63%vs 15.91%,P<0.05),while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group(50%vs 26.73%,P<0.05).Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM.IBS-C patients were found to have a higher prevalence of depression than FC patients(66.30%vs 42.42%,P<0.05).The scores for feelings of guilt,suicide,psychomotor agitation,diurnal variation,obsessive/compulsive disorder,hopelessness,self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients(P<0.05).For IBS-C(χ^(2)=5.438,P<0.05)but not FC,patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time.For IBS-C patients but not FC patients,the threshold of first constant sensation,desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety(r=0.414,r=0.404,and r=0.418,respectively,P<0.05).The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression(69.6%vs 41.9%,χ2=4.054,P<0.05).CONCLUSION Our findings highlight both overlapping and distinctive patterns of colon transit,dyssynergic patterns,anorectal sensation,psychological distress,and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population,providing valuable insights into the pathophysiological underpinnings of these disorders.

Functional constipation in children:What physicians should know

Functional constipation(FC)is considered the most common functional gastrointestinal disorder in children with a pooled global prevalence of 14.4%(95%confidence interval:11.2-17.6)when diagnosed based on the Rome IV criteria.Its pathophysiological mechanisms are thought be multifactorial and complicated,resulting in difficult management.Currently,the most effective medication,when used in parallel with toilet training,is osmotic laxatives.Children’s adherence to medication and parental concern regarding long-term laxative use are the main contributors to treatment failure.Recently,novel therapies with a high safety profile have been developed,such as probiotics,synbiotics,serotonin 5-hydroxytryptamine 4 receptor agonists,chloride channel activators,and herbal and transitional medicines;nonetheless,well-designed research to support the use of these therapies is needed.This review aims to focus on multiple aspects of FC in children,including global prevalence,pathogenesis,diagnostic criteria,tools,as well as conventional and novel treatment options,such as non-pharmacological management,including adequate fiber and fluid intake,physiotherapy,or neuromodulators.We also report that in very difficult cases,surgical intervention may be required.

Effects of probiotics and its fermented milk on constipation: a systematic review

This study reviewed clinical evidence of probiotics-mediated effects on constipation.Four databases were used in the literature searches,namely Cochrane Library,Embase,Pubmed,and Web of Science.The last retrieval time was March 2021.Collected data were analyzed by Review Manager(version 5.3)and Stata(version 14).The primary search retrieved 8418 articles after removing duplicates.Eventually,26 studies were included in the meta-analysis.Administration of probiotics signifi cantly increased stool frequency(MD:1.15 times/week;95%CI:0.59 to 1.70;P<0.0001),improved bloating(MD:-0.48;95%CI:-0.89 to-0.07;P=0.02),reduced abdominal pain(MD:-0.71;95%CI:-1.25 to-0.16;P=0.01),and improved quality of life(MD:-0.73;95%CI:-1.37 to-0.10;P=0.02).However,the clinical effect of intake of probiotics on stool consistency was non-signifi cant(MD:0.07;95%CI:-0.34 to 0.48;P=0.73).Based on our analysis,probiotic supplements were effective in relieving constipation through symptom improvement.The effectiveness of dosage forms of intervention ranked:capsules>others(tablets,powder)>fermented milk.

Association Between Constipation and a Reduction in Lower Limb Muscle Strength in Preoperative Patients with Thoracic Spinal Tumors

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs.Methods A single-center,retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021.The study involved a review of electronic medical records and radiographs and the collection of clinical data.The differences in clinical manifestations between patients with constipation and those without constipation were analyzed.Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled,including 131 patients with constipation and 96 without constipation.The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery(83.2%vs.17.7%,χ~2=99.035,P 0.001).Constipation(OR=9.522,95%CI:4.150±21.849,P 0.001)and urinary retention(OR=14.490,95%CI:4.543±46.213,P 0.001)were independent risk factors for muscle strength decline in the lower limbs.Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness.Moreover,the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.

Very early onset perinatal constipation:Can it be cow’s milk protein allergy?

Delayed passage of meconium or constipation during the perinatal period is traditionally regarded as a signal to initiate further work up to evaluate for serious diagnoses such as Hirschsprung’s disease(HD),meconium ileus due to Cystic Fibrosis,etc.The diagnosis of HD particularly warrants invasive testing to confirm the diagnosis,such as anorectal manometry or rectal suction biopsy.What if there was another etiology of perinatal constipation,that is far lesser known?Cow’s milk protein allergy(CMPA)is often diagnosed in infants within the first few weeks of life,however,there are studies that show that the CMPA allergen can be passed from mother to an infant in-utero,therefore allowing symptoms to show as early as day one of life.The presentation is more atypical,with perinatal constipation rather than with bloody stools,diarrhea,and vomiting.The diagnosis and management would be avoidance of cow's milk protein within the diet,with results and symptom improvement in patients immediately.Therefore,we discuss whether an alternative pathway to address perinatal constipation should be further discussed and implemented to potentially avoid invasive techniques in patients.This entails first ruling out CMPA with safe,noninvasive techniques with diet modification,and if unsuccessful,then moving forward with further diagnostic modalities.

Microbiota regulation in constipation and colorectal cancer

The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.

Baizhu-Baishao herb pair ameliorates functional constipation and intestinal microflora disorder in rats

Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mechanism of BZBS in the treatment of functional constipation(FC)has been little studied and remains unclear.In this study,a behavioral investigation,colon tissue morphology,enzyme-linked immunosorbent assay(Elisa)and intestinal microflora analysis have been used to illuminate the potential mechanism of the effects of BZBS on FC in a rat model.Methods:A FC rat model was constructed and BZBS was given as treatment.Observations and recordings were made of the fecal moisture content,the defecation time of the first black stool,and the rate of intestinal propulsion.Elisa was used to detect the expression levels of substance P(SP),vasoactive intestinal peptide(VIP),5-hydroxytryptamine(5-HT)in the colon.To ascertain the composition of the microbial community,a high throughput 16S ribosomal RNA(16S r RNA)gene sequencing technique was employed.Results:Oral administration of BZBS significantly ameliorated several key excretion parameters,including the time to first black stool defecation,stool water content,and the propulsion rate in the small intestine in FC rats.It increased the expression of SP,VIP and 5-HT in the colon.16S r RNA gene sequencing results showed that BZBS changed the microbial community structure,decreased the Bacteroidetes/Firmicutes ratio,increased the relative abundance of Blautia and Fusicatenibacter,and decreased the relative abundance of Ruminococcus and Roseburia.Conclusions:BZBS effectively alleviates FC and improves dysbacteriosis.

Effects of a Combination of Fu Zi and Rou Gui on Intestinal Neurotransmitters and Microflora in Rats with Slow Transit Constipation

[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.

Prevalence and Clinical Characteristics of Chronic Constipation in Senegalese Children

Introduction: Constipation is the infrequent emission of hard stools. It is common, most often of functional origin, with a prevalence ranging from 0.7% to 29.6%. The aim of our study was to investigate the prevalence of constipation in children undergoing paediatric gastroenterology. Methodology: This was a bi-centric retrospective study carried out at the Albert Royer Children’s Hospital and the Dalal Jamm Hospital Pediatrics Department. Children followed in the pediatric gastroenterology consultation during the period from January 1, 2013 to February 29, 2020 were included. Results: A total of 337 children (205 boys;60.83%) were included, representing a prevalence of 25%. The median age was 3 years 6 months. The 13 - 24 months age group was the most frequent (27.6%). Rare stools were the main reason for consultation (92.8%). Rare stools were noted in 92.88% of cases. Bristol types 1 and 2 accounted for 6.53% and 54.60% respectively. The main associated signs were abdominal pain (29.4%), followed by abdominal bloating (20.96%). Abdominal pain was functional in 73.58% of cases. Under treatment, 90.19% of children had a favorable outcome. Conclusion: Constipation is common in Senegalese children with a prevalence close to that reported in Western countries. In most case, it is functional with good prognostic.

Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

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.

Study on the mechanism of JiChuanJian in the treatment of slow-transmission constipation based on network pharmacology

Background:Slow-transit constipation remains a functional colonic disorder with the most common gastrointestinal complaint.Although JiChuanJian(JCJ)is used for treatment,little is known about its mechanism of action.We aimed to investigate the mechanism of JCJ in treating slow-transmission constipation based on network pharmacology.Methods:The chemical components and action targets of the six herbs of JCJ were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Analysis Platform.Protein targets of the chemical components were obtained from the UniProt database,whiles the disease targets were retrieved from the Gene Cards database,Disgenet,and TTD databases.A Wayne diagram was drawn and the intersected targets were imported onto the STRING website for analysis to construct protein-protein interaction target interactions.The Cytoscape software constructed protein-protein interaction to identify core targets and drug-active component-target interaction networks.The Kyoto Encyclopedia of Genes and Genomes and gene ontology enrichment analyses were performed through the DAVID analysis website.Results:A total of 55 potential drug-active components of JCJ,233 drug-active ingredient targets,3215 slow-transmission constipation-related targets,and 176 drug and disease targets were identified.The core drug-active ingredients included quercetin,beta-sitosterol,stigmasterol,kaempferol and wogonin.Through enrichment analysis in DAVID database,we obtained 236 biological processes,31 cellular components and 41 molecular functions,mainly involving serotonin binding,G-protein coupled serotonin receptor activity,and neurotransmitter receptor activity,were identified.118 pathway enrichment results were obtained after the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Therefore,we hypothesized that the active components in JCJ,such as quercetin,β-sitosterol,and stigmasterol,may treat slow transit constipation by regulating the serotonergic synapse and cyclic adenosine monophosphate signaling pathway.Conclusion:This study showed that JCJ could play a role in treating slow-transmission constipation through multiple components,targets and pathways.

The efficacy and mechanism of fecal microflora transplantation in the treatment of slow transit constipation based on metabonomics anion mode

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.

Effect of Zangfu ointment and massage therapy on functional constipation:a protocol for a randomised controlled trial

Introduction:Functional Constipation(FC)is a type of functional bowel disease that is in Clinically characterized by dysportia,decreased frequency of bowel movements,or incomplete bowel movements in the absence of irritable bowel syndrome syndrome,at least 6 months before diagnosis,and symptoms within the last 3 months.At present,commonly used drugs include enema and suppositories,laxatives,microecological preparations,gastrointestinal motility drugs and other treatments.However,the effect is limited.Traditional Chinese medicine(TCM)treatment of FC has advantages.Methods:In this randomized controlled study,244 eligible patients were randomly assigned in a 1:1 ratio to a treatment group(Zangfu ointment and massage therapy+Lactulose Oral Liquid)and a control group(Lactulose Oral Liquid)for 14 days.Number of spontaneous defecation per week and First defecation time will be used as primary outcomes,and Traditional Chinese Medicine(TCM)syndrome scores and syndrome scores,PAC-QOL form will be used as secondary outcomes.Blood routine,liver function,and renal function will be used as safety outcomes.The primary and secondary outcomes will be performed at 0th,7th,and 14th day,and the safety outcomes will be performed at 0th and 14th day.Ethics and dissemination:Ethical approval has been obtained from the Committee on Health Research Ethics of the Fangshan Hospital,Beijing University of Chinese Medicine,Beijing,People's Republic of China(FZY LK-2020-010)on September 18,2020.All patients will be provided oral and written information about the trial before screening.The study results will be disseminated by peer-review publications and conference presentations.Trial registration number:ChiCTR2000038754(registered on April 14,2021).This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited,appropriate credit is given,any changes made indicated,and the use is non-commercial.STRENGTHS AND LIMITATIONS OF THIS STUDY(1)The efficacy of the Zangfu ointment and massage therapy is evaluated in a randomised,double-blind 2-week clinical trial in FC patients.(2)Form a complete and generalizable regimen for the treatment of FC(Qi stagnation)with the Zangfu ointment and massage therapy.

A review on slow transit constipation

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.