Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.

Immune cell signatures and causal association with irritable bowel syndrome:A mendelian randomization study

BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.

Associations of daily sedentary behavior,physical activity,and sleep with irritable bowel syndrome:A prospective analysis of 362,193 participants

Background:Irritable bowel syndrome(IBS)substantially affects quality of life and requires early prevention.This study aimed to elucidate the relationships between IBS and daily behaviors,including sedentary behavior(SB),physical activity(PA),and sleep.In particular,it seeks to identify healthy behaviors to reduce IBS risk,which previous studies have rarely addressed.Methods:Daily behaviors were retrieved from self-reported data of 362,193 eligible UK Biobank participants.Incident cases were determined by self-report or health care data according to RomeⅣcriteria.Results:A total of 345,388 participants were IBS-free at baseline,during a median follow-up of 8.45 years,19,885 incident IBS cases were recorded.When examined individually,SB and shorter(≤7 h/day)or longer(>7 h/day)sleep duration were each positively associated with increased IBS risk,and PA was associated with lower IBS risk.The isotemporal substitution model suggested that replacing SB with other activities could provide further protective effects against IBS risk.Among people sleeping≤7 h/day,replacing 1 h of SB with equivalent light PA,vigorous PA,or sleep was associated with 8.1%(95%confidence interval(95%CI):0.901-0.937),5.8%(95%CI:0.896-0.991),and 9.2%(95%CI:0.885-0.932)reduced IBS risk,respectively.For people sleeping>7 h/day,light and vigorous PA were associated with a 4.8%(95%CI:0.926-0.978)and a 12.0%(95%CI:0.815-0.949)lower IBS risk,respectively.These benefits were mostly independent of genetic risk for IBS.Conclusion:SB and unhealthy sleep duration are risk factors for IBS.A promising way to mitigate IBS risk for individuals sleeping≤7 h/day and for those sleeping>7 h/day appears to be by replacing SB with adequate sleep or vigorous PA,respectively,regardless of the genetic predisposition of IBS.

Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome:A Systematic Review and Meta-Analysis

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September 2023.Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified.We estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the curve.Results Four studies were included.The pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for IBS.However,limited high-quality data make the results'validity and applicability questionable.There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.

Lactobacillus plantarum AR495 improves stress-induced irritable bowel syndrome in rats by targeting gut microbiota and Mast cell-PAR2-TRPV1 signaling pathway

Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.

Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Fecal microbiota transplantation for irritable bowel syndrome:Current evidence and perspectives

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology.We focus specifically on the mechanisms underlying the effects of fecal microbiota transplantation(FMT)for irritable bowel syndrome(IBS),the factors which affect the outcomes of FMT in IBS patients,and challenges.FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS.The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials,yielding divergent outcomes.The current frontier in this field seeks to elucidate these variations,underscore the existing knowledge gaps that necessitate exploration,and provide a guideline for successful FMT implementation in IBS patients.At the same time,the application of FMT as a treatment for IBS confronts several challenges.

Unveiling the intricacies of irritable bowel syndrome

Irritable bowel syndrome(IBS)remains a challenging condition both for patients and clinicians,characterized by its chronic nature and the elusive complexity of its underlying mechanisms.The multifaceted relationship between the neuroendocrine axis,gut microbiota,and inflammatory response has emerged as a focal point in recent research,offering new insights into the pathophysiology of IBS.The neuroendocrine axis plays a crucial role in maintaining the delicate balance between the brain and the gut,often referred to as the“gut-brain axis”.This bidirectional communication is essential for regulating gastrointestinal function,stress responses,and overall homeostasis.Dysregulation of this axis,as highlighted by elevated cortisol and serotonin levels in IBS patients,suggests that neuroendocrine imbalances may significantly contribute to the severity of gastrointestinal symptoms.These findings underscore the need for a broader understanding of how stress and emotional factors influence IBS,potentially guiding more effective,personalized treatment approaches.Equally important is the role of the gut microbiota,a diverse and dynamic ecosystem that directly impacts gut health.This dysbiosis disrupts gut function and appears to exacerbate the neuroendocrine and inflammatory responses.These findings align with the growing recognition that gut microbiota is a critical player in IBS,influencing both the disease's onset and progression.

Alleviative effects of Bacillus coagulans strains on irritable bowel syndrome-unraveling strain specificity through physiological and genomic analysis

The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.

Current Insights on Vitamin D Intake, Status and Symptoms of Irritable Bowel Syndrome: A Narrative Review

The association between Vitamin D and IBS has attracted growing interest because of vitamin D’s involvement in immune system function and reduction of inflammation. IBS, a prevalent gastrointestinal condition marked by symptoms such as stomach pain, bloating, and changed bowel habits, implies that sufficient levels of Vitamin D may impact the symptomatology and quality of life associated with IBS. This review aimed to unveil current insights on vitamin D intake, status and symptoms of irritable bowel syndrome. A search was conducted on Embase, Scopus, Medline, and Cochrane Library, as well as a reference list of relevant studies. This paper also examined the current therapeutic practices for using vitamin D in the management of IBS. Although several studies demonstrate a positive association between vitamin D administration and the alleviation of IBS symptoms, the data is not yet definitive. Moreover, the review emphasised the necessity for additional rigorous clinical studies to determine a definitive therapeutic function of vitamin D in IBS based on the literature. The role of vitamin D in the modulation of gut health, particularly in IBS, has garnered significant attention due to its potential impact on both inflammation and the integrity of the gut barrier. Vitamin D, acting as a hormone precursor, is recognised for its crucial involvement in maintaining calcium balance and promoting bone health.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

Based on network pharmacology,molecular docking and experimental validation to reveal the potential molecular mechanism of quercetin for the treatment of diarrheal irritable bowel syndrome

Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network pharmacology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,thereby treating IBS-D.

New paradigm of oral rehydration in patients affected by irritable bowel syndrome with chronic diarrhea

Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.

Efficacy and tolerability of chitin-glucan combined with simethicone(GASTRAP^(■)DIRECT)in irritable bowel syndrome:A prospective,open-label,multicenter study

BACKGROUND Irritable bowel syndrome(IBS),defined according to the Rome IV diagnostic criteria,is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel habits.First-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic gain.GASTRAP^(■)DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action.AIM To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with IBS.METHODS In this prospective,multicenter,open-label trial,120 patients with IBS received three sticks of GASTRAP^(■)DIRECT(1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone)per day for 4 weeks.The primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)4.The analysis was performed using the per-protocol set.Cardinal symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were evaluated.RESULTS Overall,100 patients were evaluated.At W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,P<0.0001).Similar improvements were observed for bloating[8.0±1.7 vs 4.7±2.9,P<0.0001;60%(95%CI:50-70)responders],abdominal distension[7.2±2.1 vs 4.4±3.1,P<0.0001;53%(95%CI:43-63)responders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,P<0.0001;54%(95%CI:44-64)responders].Stool consistency improved in most patients(90%and 57%for patients with liquid and hard stools,respectively).Overall,42%of patients with defecatory disorders reported very much/considerable improvements by W2.No severe adverse event occurred,and tolerability was rated“good”or“very good”by 93%of patients.CONCLUSION GASTRAP^(■)DIRECT is safe and well tolerated,alleviating IBS symptoms rapidly in 2 weeks.This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.

Link between irritable bowel syndrome,depression,and colorectal cancer risk in young patients:Age-matched nationwide populationbased study

BACKGROUND There exists a link between irritable bowel syndrome(IBS)and depression.Similarly,chronic depression is known to increase the risk of cancer in general.In this population-based analysis,we investigated the prevalence and the odds of colorectal cancer(CRC)in young-depressed patients with IBS.AIM To investigate the relationship between IBS and CRC in young,depressed patients using a nationally representative United States inpatient sample.METHODS The 2019 National Inpatient Sample was used to identify young(18-44 years)patients admitted with comorbid depression in the presence vs absence of IBS using relevant International Classification of Diseases,Tenth Revision,Clinical Modification codes.Primary endpoint was the prevalence and odds of CRC in age matched(1:1)youngdepressed cohort hospitalized with IBS(IBS+)vs without IBS(IBS-).Multivariable regression analysis was performed adjusting for potential confounders.RESULTS Age-matched(1:1)young-depressed IBS+(83.9%females,median age 36 years)and IBS-(65.8%females,median age 36 years)cohorts consisted of 14370 patients in each group.IBS+cohort had higher rates of hypertension,uncomplicated diabetes,hyperlipidemia,obesity,peripheral vascular disease,chronic obstructive pulmonary disease,hypothyroidism,prior stroke,prior venous thromboembolism,anxiety,bipolar disorder,and borderline personality disorder(P<0.005)vs the IBS-cohort.However,prior myocardial infarction,acquired immunodeficiency syndrome,dementia,smoking,alcohol abuse,and drug abuse(P<0.005)are high in IBS-cohort.The rate of CRC was comparable in both cohorts[IBS+n=25(0.17%)vs IBS-n=35(0.24%)].Compared to the IBS-cohort,the odds ratio(OR)of developing CRC was not significantly higher[OR 0.71,95% confidence interval(CI)0.23-2.25]in IBS+cohort.Also,adjusting for baseline sociodemographic and hospital characteristics and relevant comorbidities,the OR was found to be non-significant(OR 0.89,95%CI 0.21-3.83).CONCLUSION This nationwide propensity-matched analysis revealed comparable prevalence and risk of CRC in youngdepressed patients with vs without IBS.Future large-scale prospective studies are needed to evaluate the long-term effects of depression and its treatment on CRC risk and outcomes in IBS patients.

Clinical Effect of Modified Shengyang Yiwei Decoction in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome due to Spleen and Stomach Weakness

Objective:To explore the therapeutic effect of Shengyang Yiwei Decoction in patients with diarrhea-predominant irritable bowel syndrome(IBS)due to spleen and stomach weakness.Methods:40 patients with diarrhea-predominant IBS who were treated from April 2018 to April 2020 were taken as samples.TCM(traditional Chinese medicine)syndrome differentiation found that they were all due to spleen and stomach weakness.They were randomly divided into two groups.Group A was treated with modified prescriptions of Shengyang Yiwei Decoction,while Group B was treated with Western medicine.The therapeutic effects in the two groups were compared.Results:The treatment efficacy in Group A was higher than that in Group B(P<0.05);the symptom scores of Group A such as loose stools,chills,physical weakness,poor appetite,and abdominal distension after meals were all lower than those in Group B(P<0.05);the SF-36(36-Item Short Form Health Survey)scores of patients with diarrhea-predominant IBS in Group A were higher than those in Group B(P<0.05);the treatment satisfaction of Group A was higher than that of Group B(P<0.05).Conclusion:Treatment of diarrhea-predominant IBS patients with spleen and stomach weakness by Shengyang Yiwei Decoction can promote the disappearance of gastrointestinal discomfort symptoms,improve the quality of life,and enhance treatment efficacy.Hence,it is an efficient and feasible treatment for diarrhea-predominant IBS due to spleen and stomach weakness.

Current Research Status of Traditional Chinese Medicine External Treatment for Diarrhea Type Irritable Bowel Syndrome

Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeutic effects,while traditional Chinese medi‐cine has unique advantages in relieving IBS-D symptoms and preventing recurrence.In recent years,especially with external treatment of traditional Chinese medicine,it has become a new treatment direction in clinical practice and has achieved good therapeutic effects.This article will provide a review of recent research on the treatment of IBS-D using traditional Chinese medicine external treatment methods.

Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome

BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome(IBS-D);however,the certainty of evidence is low.Wellpowered randomized controlled dose-ranging trials are warranted on promising single-strain candidates.AIM To investigate the clinical efficacy of Lactiplantibacillus plantarum(L.plantarum)Lpla33(DSM34428)in adults with IBS-D.METHODS This is a randomized,double-blind,placebo-controlled,multi-center,and doseranging study.Three hundred and seven adults,18-70 years of age,with IBS-D,according to Rome IV criteria,were allocated(1:1:1)to receive placebo or L.plantarum Lpla33 at 1×10^(9)(1B)or 1×10^(10)(10B)colony-forming units/d over an 8-wk intervention period.The primary outcome was the change in IBS severity scoring system(IBS-SSS)total score after 8 wk,while secondary and exploratory outcomes included abdominal pain severity,IBS related quality of life,stool and microbial profile,and perceived stress.RESULTS IBS-SSS was significantly reduced,after 8 wk,in participants receiving L.plantarum 1B(-128.45±83.30;P<0.001)and L.plantarum 10B(-156.77±99.06;P<0.001),compared to placebo(-58.82±74.75).Further,a dose-ranging effect was observed,with a greater absolute reduction in the L.plantarum 10B group(P<0.05).A reduction in sub-scores related to abdominal pain,abdominal distension,bowel habits,and quality of life was observed in both L.plantarum groups compared to placebo(P<0.001).Further,62.5%and 88.4%of participants administered L.plantarum 1B and 10B,respectively,were classified as stool consistency responders based on a reduction in diarrheal stool form,as compared to 26.3%in the placebo group(P<0.001).In contrast,no significant shifts were observed in microbial diversity.CONCLUSION L.plantarum Lpla33(DSM34428)is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.

Adenosine 2A receptor contributes to the facilitation of postinfectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway

BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.

Contribution to the Study of Irritable Bowel Syndrome in Medical Students at the University of Parakou in Republic of Benin

Introduction: Irritable bowel syndrome is the most common functional gastrointestinal disorder. The objective of this work is to contribute to improving the medical follow-up of medical students at the University of Parakou through a study of irritable bowel syndrome. Study Methods: This was a descriptive and analytical cross-sectional study with prospective data collection. Data were collected from medical students from May 2018 to July 2018 using a pre-established questionnaire. Sampling was probabilistic using a two-stage survey. The diagnostic tools were: Rome IV criteria, Bristol scale and HAD (hospital anxiety and depression) scale. Data analysis was performed using Epi Info 7.1.3.14 software. CDC. Results: Thirty-two (7.55%) of the 424 students included had irritable bowel syndrome. Out of the 32 students with IBS, 24 (75%) were female. Their average age was 21.38 ± 2.39 years. For 24 students (75%), the symptoms occurred at the same time as exam preparation or the intense course period. Of the 32 students with IBS, 1 (3.12%) was regularly physically active. In this series, 8 students (28%) consulted a doctor for their symptoms. The factors associated with this syndrome were female sex (p = 0.022), sleep disorders (p = 0.008) and the presence of a doubtful depression (p = 0.021). Absenteeism due to irritable bowel syndrome was noted in 18 (56.25%) students. Conclusion: Irritable bowel syndrome is a common condition among medical students in Parakou. Support for better management of psychological disorders could improve the quality of life of these students.