Irritable Bowel Syndrome With Diarrhea Research Articles

A Review of Pharmacologic and Non-Pharmacologic Therapies in the Management of Irritable Bowel Syndrome: Current Recommendations and Evidence.

Irritable bowel syndrome (IBS) is a highly prevalent and debilitating disorder of gut-brain interaction (DGBI) affecting millions globally. It imposes a significant burden on healthcare systems and is a leading cause of workplace absenteeism. IBS is classified into several subtypes based on predominant presenting symptoms, including IBS with constipation (IBS-C) and IBS with diarrhea (IBS-D), with each requiring targeted approaches to treatment. Some treatments, such as psychotherapy, dietary intervention, and medications like tricyclic antidepressants, are nonspecific and recommended for managing IBS symptoms across all subtypes. In contrast, therapies like secretagogues for IBS-C and eluxadoline or rifaximin for IBS-D are subtype-specific. However, many IBS treatments carry conditional recommendations and are based on low-certainty evidence, emphasizing the need for further research to expand the available treatment options. This review compares the latest IBS management guidelines from the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), British Society of Gastroenterology (BSG), and European Society for Neurogastroenterology and Motility (ESNM). Pharmacologic and non-pharmacologic therapies, including established and emerging interventions, will be explored to provide a comprehensive guide to management.

Efficacy of acupuncture treatment for diarrhea-predominant irritable bowel syndrome with comorbid anxiety and depression: A meta-analysis and systematic review.

Presently, a diverse range of Western medical interventions are accessible for the management of irritable bowel syndrome with diarrhea (IBS-D) concomitant with comorbid anxiety and depression. However, the concomitant adverse effects have also surfaced, exerting strain on healthcare resources and the socio-economic structure. In recent times, the benefits of acupuncture in the management of IBS-D with coexisting anxiety and depression have become progressively evident. Nevertheless, a paucity of evidence-based medicine exists to substantiate the utilization of acupuncture for the treatment of IBS-D with anxiety and depression. The objective of this study is to examine the effectiveness of acupuncture as an intervention for IBS-D with comorbid anxiety and depression. We searched 7 databases, including the Chinese Journal Full-text Database, Wanfang Academic Journals Full-text Database, VIP Chinese Scientific Journals Full-text Database, China Biomedical Literature Database, PubMed, Embase, and Cochrane Library, for randomized controlled trials (RCTs) related to acupuncture treatment for IBS with anxiety and depression, published from database inception to August 1, 2023. RevMan 5.4 and Stata 17.0 software were used for meta-analysis of relevant outcome measures. This study included a total of 16 RCTs, involving 1305 IBS-D patients (691 in the experimental group and 614 in the control group). The meta-analysis results showed that compared to oral medication, acupuncture therapy improved HAMD scores (MD = 0.88, 95% CI = [0.68, 1.07], P < .00001), HAMA scores (MD = 2.32, 95% CI = [1.70, 2.93], P < .00001), self-rating anxiety scale scores (MD = 11.67, 95% CI = [10.85, 12.49], P < .00001), SDS scores (MD = 9.84, 95% CI = [8.52, 11.16], P < .00001), IBS-SSS scores (MD = 37.48, 95% CI = [12.17, 62.78], P = .004), overall response rate (MD = 1.27, 95% CI = [1.20, 1.35], P < .00001), and relapse rate (MD = 0.27, 95% CI = [0.16, 0.47], P < .00001) in patients with IBS-D comorbid with anxiety and depression. Acupuncture treatment has a definite and beneficial effect on IBS-D patients with comorbid anxiety and depression.

Stress triggers irritable bowel syndrome with diarrhea through a spermidine-mediated decline in type I interferon.

Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.

Transcriptomic Module Discovery of Diarrhea-Predominant Irritable Bowel Syndrome: A Causal Network Inference Approach.

Irritable bowel syndrome with diarrhea (IBS-D) is the most prevalent subtype of IBS, characterized by chronic gastrointestinal symptoms in the absence of identifiable pathological findings. This study aims to investigate the molecular mechanisms underlying IBS-D using transcriptomic data. By employing causal network inference methods, we identify key transcriptomic modules associated with IBS-D. Utilizing data from public databases and applying advanced computational techniques, we uncover potential biomarkers and therapeutic targets. Our analysis reveals significant molecular alterations that affect cellular functions, offering new insights into the complex pathophysiology of IBS-D. These findings enhance our understanding of the disease and may foster the development of more effective treatments.

Translational evaluation of Gelsectan® effects on gut barrier dysfunction and visceral pain in animal models and irritable bowel syndrome with diarrhoea.

Gelsectan® is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan® on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions. Animals: Wistar rats received gavage with XOS, XG+PPGS or XG+PPGS+XOS, as a single dose or for 7days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to 51Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan® was administered to IBS-D patients for 12weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNFα, Interferon IFNγ were evaluated by histology/immunohistochemistry and ELISA assays, respectively. Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG+PPGS+XOS failed to reverse PRS, but 7days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan® treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan® restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan® treatment. IFNγ tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D. Gelsectan® prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan® can be considered as an effective therapy for IBS-D symptoms.

Low dose rifaximin combined with N-acetylcysteine is superior to rifaximin alone in a rat model of IBS-D: a randomized trial

Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.

Animal models with characteristics of irritable bowel syndrome with diarrhea: current applications and future perspectives.

Irritable bowel syndrome with diarrhea (IBS-D) is a common intestinal condition that significantly impacts work efficiency and quality of life. The use of animal models is crucial for delving into the pathophysiology of IBS-D and exploring therapeutic options. However, a wide variety of animal models for IBS-D has been used in previous studies, posing a considerable challenge for researchers in selecting a suitable model. In this review, using the Web of Science database, we searched IBS-D-related research spanning from 2014 to 2023; described the differences in animal strains and modeling methods among various IBS-D features recapitulating models; summarized the frequency of model usage, pathogenesis, and pathological characteristics of these models; and discussed their current applications, limitations, and future perspectives. The objective is to offer theoretical guidance for future researchers, aiding them in choosing suitable animal models based on their experimental designs.

Rifaximin: A Comprehensive Review of Structure, Uses, Mechanisms of Action, and Assay Methods

Rifaximin, a derivative of rifamycin, has emerged as a promising therapeutic tool in gastroenterology. This review explores rifaximin's intricate molecular structure and pharmacokinetic properties, highlighting its minimal systemic absorption and targeted action within the gut. The multifaceted mechanisms of action, including direct antibacterial effects and modulation of gut microbiota, are discussed. The review then examines the efficacy of rifaximin in treating various gastrointestinal disorders like traveler's diarrhea, Irritable Bowel Syndrome with Diarrhea (IBS-D), and Small Intestinal Bacterial Overgrowth (SIBO). Dosage recommendations and the well-tolerated safety profile of rifaximin are presented. Finally, the importance of quality control measures using techniques like HPLC and spectroscopy is emphasized to ensure the drug's effectiveness and safety.

MiR-155 and miR-21 as Diagnostic and Therapeutic Biomarkers for Ulcerative Colitis: There Is Still a Long Way to Go.

(1) Elucidating the role of miRNAs (miRs) in ulcerative colitis may provide new insights into disease pathogenesis, diagnosis, treatment, and monitoring We aimed to investigate whether plasma levels of miR-21-5p and miR-155-5p may be used to differentiate between patients with organic disease such as ulcerative colitis (UC) and Clostridioides difficile infection (CDI), and patients with functional disease such as irritable bowel syndrome with diarrhea (IBS-D). (2) Serological samples were collected to quantify miR-155 and -21 expression, which was carried out through quantitative real-time polymerase chain reaction (qRT-PCR), from 84 patients: 34 with acute UC (group 1), 17 with CDI (group 2), and 33 with IBS-D (control group). (3) In this study, we found that the expression levels of miR-155-5p were almost the same for the two conditions and the control group (UC: 4.22 ± 1.61, CDI: 3.94 ± 1.62, IBS-D: 4.26 ± 1.26), with no significant differences either for ΔCt- or for ΔΔCt-derived parameters (p = 0.74 and p = 0.73, respectively). For miR-21, ΔCt levels presented significantly higher values among the ulcerative colitis group (p < 0.01), but the most important expression fold change was noticed in patients with CDI (UC:4.11 ± 8,46, CDI: 4.94 ± 9.68, IBS-D: 2.83 ± 5.41). (4) Circulating miR-155 and miR-21 were upregulated in UC, CDI, and IBS-D, but differentiation was not possible among them. But their involvement in the pathogenesis of the three diseases makes them suitable for improving the accuracy of diagnosis and facilitating the development of personalized treatment strategies.

Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis.

The efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy. By conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM's effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database. Twenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = -1.08, 95% CI (-1.30, -0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, -0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, -0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, -0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance. Chinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM's therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.

Irritable Bowel Syndrome in Veterans With Gulf War Illness Evaluated at VA's War-Related Illness and Injury Study Center.

Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms. We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020. We applied Centers for Disease Control (CDC) criteria to determine the prevalence of severe GWI. IBS was identified using Rome IV diagnostic criteria (current IBS) and veterans' self-reported "history of physician-diagnosed IBS." We examined associations between IBS and GWI using bivariate analyses and multivariable logistic regression. Among the N = 578 GWVs evaluated by the WRIISC, severe GWI (71.8%), history of physician-diagnosed IBS (50.3%) and current IBS (42.2%) were all highly prevalent. Nearly half of GWVs with severe GWI met Rome criteria for IBS (45.8%), and over half reported a history of physician-diagnosed IBS (56.1%). In multivariable models, severe GWI was significantly associated both with current IBS (adjusted odds ratio (aOR): 1.68, 95% CI: 1.11, 2.54) and with veteran-reported history of physician-diagnosed IBS (aOR: 2.15, 95% CI: 1.43, 2.23). IBS with diarrhea (IBS-D) was the most common subtype among GWVs with current IBS (61.1%). However, IBS-mixed affected a significantly greater proportion of veterans with severe GWI, compared to veterans who did not have severe GWI (P = .03). More than 20 years after the Persian Gulf War, our findings indicate a high degree of comorbidity between severe GWI and IBS among deployed GWVs seeking care for unexplained illnesses. Our results suggest GWVs with GWI should be screened for IBS for which evidence-based treatments are available and could potentially reduce symptom burden. Conversely, symptoms of IBS should trigger additional evaluation for non-gastrointestinal symptoms in deployed Gulf War veterans to identify possible GWI and ensure a comprehensive approach to care.

Is a Simplified, Less Restrictive Low FODMAP Diet Possible? Results from a Double-Blind, Pilot Randomized Controlled Trial

A low fermentable oligo-, mono-, di-saccharides, and polyols (FODMAPs) diet (LFD) is the most evidence-based dietary therapy for patients with irritable bowel syndrome (IBS).1 However, the current step-down approach to the LFD has significant limitations including being costly, complex, time-consuming, and associated with reduced dietary intake of some micronutrients.2-4 Recently, a step-up approach has been proposed that restricts only a limited number of FODMAPs initially, evaluating symptom response and restricting additional FODMAPs only if necessary.2,5,6 In a double-blind trial, fructans and galacto-oligosaccharides were found to be the most likely FODMAP subgroups to trigger IBS symptoms.7 To date, no study has compared the efficacy of a traditional LFD restriction phase with a more targeted or simplified restriction phase. In a double-blind, pilot-feasibility randomized controlled trial, we compared the efficacy of a 4-week FODMAP-simple restriction phase (eliminating solely fructans and galactooligosaccharides) and a traditional LFD restriction phase in patients with IBS with diarrhea (IBS-D) (ClinicalTrials.gov registration number NCT05831306).

Treatment-Free Interval: A Novel Approach to Assessing Real-World Treatment Effectiveness and Economic Impact Among Patients with Irritable Bowel Syndrome with Diarrhea.

Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA. Adult patients (18-64years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics® Plus database (10/01/2015-12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences. There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30days (76.2% vs. 66.7%), ≥ 60days (67.0% vs. 47.0%), ≥ 90days (61.0% vs. 38.7%), ≥ 180days (51.7% vs. 31.0%), and ≥ 240days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30days, mean TFI durations were 8.3 and 6.0months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437; p = 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250; p < 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1million per year or $0.18per-member-per-month. This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea

Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. Methods: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. Results: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. Conclusion: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

A Mini Literature Review of Probiotics: Transforming Gastrointestinal Health Through Evidence-Based Insights.

As our understanding of the intricate interaction between gut bacteria and human health continues to expand, so too has interest in the ability of probiotics to manage gut microbiota and confer multiple health benefits to the host. The mini literature review focuses on the expanding potential of the use of probiotics in GI health, with a focus on probiotics' potential therapeutic advantages in a variety of gastrointestinal (GI) illnesses. Probiotics play a significant role in managing diarrhea and symptoms of irritable bowel syndrome with diarrhea (IBS-D) by modulating gut microbial communities. Specific probiotic strains have been found to reduce the abundance of harmful bacteria, regulate inflammatory markers like interleukin 6, and improve GI symptoms such as abdominal discomfort and stool consistency. Additionally, probiotic blends have shown potential for preventing GI infections and alleviating GI pain in IBS-D patients. Studies have demonstrated that certain multi-strain probiotics, including Bifidobacterium and Lactobacillus species, can significantly increase the frequency of bowel movements and reduce the proportion of individuals experiencing constipation. It has also been found that probiotic supplementation may reduce the incidence of postoperative complications and mortality, particularly in patients undergoing colorectal adenocarcinoma surgery. Additionally, probiotics have been associated with decreased levels of pro-inflammatory cytokines and improved clinical outcomes in patients with colorectal cancer. Furthermore, probiotics have been associated with enhanced digestive tolerance, reduced GI inflammation, and prolonged clinical remission in certain UC patients. Studies have also shown that probiotics, administered either directly to infants or pregnant women during the perinatal stage, can alleviate symptoms such as inconsolable crying and irritation associated with infant colic, improve bowel movement frequency in cases of functional constipation, and enhance overall conditions in premature infants, including reducing regurgitation and improving feeding tolerance. The review addresses both encouraging results and challenges with probiotic therapy, while also arguing for more studies to elucidate underlying mechanisms and enhance therapeutic techniques. As we traverse the complex field of probiotic therapy in the treatment of GI illnesses, researchers, physicians, and other healthcare professionals can benefit from the informative information provided by this study.

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 administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded. RESULTS Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia. Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist. CONCLUSION Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.

Journal of Clinical Gastroenterology Lectureship Dubai 2022 : Management of Irritable Bowel Syndrome With Diarrhea.

Irritable bowel syndrome (IBS) with diarrhea (IBS-D) affects ~1% of the general population and is characterized by abdominal pain associated with diarrhea. IBS-D symptoms significantly impact the quality of life of patients. Major uncertainties remain regarding the optimal management of these patients. Several therapies have been investigated over the years for the treatment of IBS-D. In the initial management, commonly prescribed approaches with an effect on global IBS symptoms include a low Fermentable Oligo-, Di-, Mono-Saccharides and Polyols diet and probiotics, while antispasmodics are used for targeting abdominal pain and loperamide for diarrhea only. Additional therapeutic options for the relief of global IBS symptoms include rifaximin, 5-HT 3 antagonists, gut-directed psychological therapies, and eluxadoline, while tricyclic antidepressants can target abdominal pain and bile acid sequestrants diarrhea. Promising evidence exists for the use of mesalazine and fecal microbiota transplantation in IBS-D, although further evidence is needed for definitive conclusions regarding their efficacy.

Electroacupuncture Improving Intestinal Barrier Function in Rats with Irritable Bowel Syndrome Through Regulating Aquaporins.

Intestinal mucosal barrier dysfunction plays a crucial role in the pathogenesis of irritable bowel syndrome with diarrhea (IBS-D). In order to explore the mechanism of electroacupuncture (EA) treatment on intestinal mucosal barrier, this study observed the effect of EA on aquaporins (AQPs), tight junctions (TJs), NF-κB pathway and the gut microbiota in IBS-D rats. The IBS-D model was established by acetic acid enema combined with chronic restraint method. The effects of EA on the treatment of IBS-D were examined by the abdominal withdrawal reflex score, Bristol's fecal character score, fecal water content, small intestine propulsion rate and HE staining. AQPs, TJs and inflammation-related molecular mechanisms were explored. The fecal samples were applied for 16S rRNA sequencing to assess the effect of EA intervention to the intestinal bacterial abundance. EA reduced intestinal sensitization, restored intestinal motility and improved inflammatory cell infiltration. Furthermore, EA improved intestinal inflammation and flora environment significantly, inhibited NF-κB signaling and inflammatory factors (IL-1β and TNF-α). It can also increase the gene and protein expression of AQPs (AQP1, AQP3, and AQP8) and the gene levels of TJs (ZO-1 and Occludin). EA has an inhibitory effect on the NF-κB signaling pathway, and regulates the proteins of AQP1, AQP3, AQP8, and TJs to restore the balance of water metabolism and intestinal permeability in IBS-D, which also restored the function of the intestinal mucosa by regulating the intestinal flora.

Anxiety-Related Factors Associated With Symptom Severity in Irritable Bowel Syndrome in Jazan, Saudi Arabia.

This study in Jazan, Saudi Arabia aims to identify anxiety-related factors associated with symptom severity in irritable bowel syndrome (IBS). IBS is a common gastrointestinal disorder causing abdominal pain and altered bowel habits. The prevalence of IBS in Saudi Arabia is estimated to be 10%-20% among the general population. Therefore, the present study aimed todetermine anxiety-related factors associated with symptom severity in irritable bowel syndrome in Jazan, Saudi Arabia. Understanding these factors will provide insights into the overall impact of IBS on patients' quality of life. The study utilized a cross-sectional, descriptive observational design to examine the general population in Jazan, Saudi Arabia. The sample size of 385 individuals was calculated based on the population size and desired error margin. A convenience sampling technique was employed to select participants who met the inclusion criteria. A validated anonymous self-administered electronic survey was distributed through social media channels. The survey consisted of four sections gathering demographic information, personal risk factors, IBS types with anxiety and risk factors, and a questionnaire to determine the level of anxiety. A pilot study was conducted to improve the survey's clarity. Ethical considerations were followed, and data were analyzed using Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY, USA). Descriptive statistics and significance tests were performed. A study with 637 participants found a 31.08% prevalence of IBS, which was more common in females. Participants with IBS had a higher rate of chronic disease. There were no significant differences in demographic factors between IBS and non-IBS participants. The duration of IBS diagnosis varied, with the majority of IBS with diarrhea (IBS-D) sufferers being diagnosed five years prior. Symptom severity differed among IBS types, with those with an unspecified type reporting the highest percentage of severe symptoms. IBS types were also correlated with anxiety levels, with IBS-D sufferers reporting moderate anxiety and those with an unspecified type reporting severe anxiety. A study with 637 participants found the prevalence of IBS to be 31.08%, with higher rates in females. IBS was associated with chronic diseases and higher anxiety levels. The findings emphasize the need for comprehensive management of IBS, including psychological interventions and dietary modifications, to improve patients' overall health and quality of life. Further research on genetic and modifiable risk factors is needed.

Moxibustion ameliorates visceral hypersensitivity by regulating hypothalamus-spinal cord-colon axis in rats with irritable bowel syndrome with diarrhea.

To observe the effect of moxibustion intervention on the hypothalamus-spinal cord-colon axis of rats with irritable bowel syndrome with diarrhea (IBS-D) and explore the mechanism of moxibustion in improving visceral hypersensitivity in rats with IBS-D. A total of 36 SD rats were randomly divided into normal, model, and moxibustion groups, with 12 rats in each group. The IBS-D model was established by maternal separation + acetic acid stimulation + chronic restraint. Rats of the moxibustion group received bilateral moxibustion on "Tianshu" (ST25) and "Shangjuxu" (ST37) for 15 min, once a day for 7 consecutive days. The body weight, loose stool rate, and minimum threshold volume of abdominal withdrawal reflex (AWR) were measured before and after moxibustion intervention, respectively. The histopathological changes in the colon tissue were observed after HE staining. The number of colonic mucosal mast cells (MCs) was measured by toluidine blue staining. The activation of MCs was determined by tryptase positive expression level and examined by immunohistochemical staining. The content, protein and mRNA expression levels and positive expression levels of corticotropin releasing factor (CRF), substance P (SP), and calcitonin gene-related peptide (CGRP) in the hypothalamus, spinal cord and colon tissues were measured by ELISA, Western blot, real-time fluorescent quantitative PCR and immunofluorescence staining, respectively. Compared with the normal group, the loose stool rate was increased (P<0.01)；the body weight and minimum threshold volume of AWR were decreased (P<0.01)；the inflammatory infiltration of colon tissues was obvious；the number of MCs and positive expression level of tryptase in the colon tissue were increased (P<0.01)；the contents, positive expression le-vels, protein and mRNA expression levels of CRF, SP and CGRP in the hypothalamus, spinal cord and colon tissues were increased (P<0.01, P<0.05) in the model group. After the intervention, compared with the model group, all these indicators showed opposite trends (P<0.01, P<0.05) in the moxibustion group. Moxibustion can improve visceral hypersensitivity in rats with IBS-D, and its mechanism may be related to regulating the hypothalamic-spinal-colon axis to reduce the release of CRF, SP and CGRP, and thus to inhibite MC in colon tissue.