Irritable Bowel Syndrome With Diarrhea Research Articles

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.

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. 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 (CUMS). 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. 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.

Getting the BS out of Irritable Bowel Syndrome with Diarrhea (IBS-D): Let's Make a Diagnosis.

Irritable bowel syndrome with diarrhea (IBS-D) is diagnosed when chronic symptoms of abdominal pain accompany loose stools, and alarm features, such as fever, anemia, rectal bleeding, and weight loss are absent. This combination of symptoms makes structural disorders, such as inflammatory bowel disease or cancer, unlikely, but does not exclude other conditions that cause these symptoms. The question is whether making a "positive diagnosis" of IBS-D based on symptoms alone and instituting therapy based on that diagnosis still makes sense. Clinical observations suggest that at least two-thirds of cases of IBS-D can be explained by three mechanisms: a) food intolerances (~ 30-40%), b) bile acid diarrhea (~ 20-30%), and c) disturbed microbial flora (~ 15-20%). Other conditions that are less frequent but can cause IBS symptoms or be confused with IBS include: celiac disease, microscopic colitis, mastocytosis/mast cell activation, and drug side-effects. Many cases of IBS-D have a discoverable, underlying cause that can direct therapy more efficiently.

Atractylodes macrocephala-Paeonia lactiflora Class Formula for the Treatment of Irritable Bowel Syndrome: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.

Previous meta-analyses suggested that Chinese herbal medicine (CHM) is effective for irritable bowel syndrome (IBS). Formulas with Atractylodes macrocephala and Paeonia lactiflora as the core pairs have been widely used by traditional Chinese medicine (TCM) practitioners for the treatment of IBS. We aimed to examine the efficacy and safety of the Atractylodes macrocephala-Paeonia lactiflora class formula (A-P CHM) for IBS through a meta-analysis and trial-sequential analysis (TSA). The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023439087. We searched seven databases for data up to May 23, 2023. The primary outcome was global IBS symptom relief. The secondary outcomes included theIBS severity scoring system (IBS-SSS) score and treatment-related adverse events. The relative ratio (RR) (dichotomous variables), the standardized mean difference (SMD) (continuous variables), the number needed to treat (NNT), the number needed to harm (NNH), and the required information size (RIS) were calculated. Twenty-four eligible articles with 3,768 participants were included. Thirteen trials were at low risk of bias (RoB). Compared with placebo or Western medication, A-P CHM was associated with a significantly higher proportion of relief of global IBS symptoms. The TSA analysis verified the primary outcome. For the secondary outcome, the A-P CHM IBS-SSS score was lower than Western medication or placebo at the end of the treatment, which was further confirmed by the TSA analysis. We asserted that A-P CHM might be a potential candidate for patients with IBS, especially for IBS-D. It may provide a theoretical basis for future optimization of irritable bowel syndrome with diarrhea (IBS-D) herbal formulas. The overall certainty of the evidence was not high; more tightly designed randomized controlled trials (RCTs) are required in the future.

COLPLATIR® as a Novel Therapeutic Adjuvant for the Management of Irritable Bowel Syndrome (IBS)

Irritable Bowel Syndrome (IBS) is a chronic disorder of the gastrointestinal system characterized by abdominal pain or discomfort and associated with different comorbidities like fibromyalgia, chronic pelvic pain, gastroesophageal reflux disease, anxiety and depression. In this study, the effects of COLPLATIR®, a nutraceutical product with a patented technology named BUTIRESOLV®, were investigated. In vivo and Ex-vivo analysis were carried out on IBS with diarrhoea (IBS-D) mouse model by intracolonic administration of Oil of Mustard (OM). Positive results have been obtained, thus demonstrating that the nutraceutical COLPLATIR® could reduce the abnormalities in intestinal motility, as observed in IBS.

Luteolin Attenuates Oxidative Stress and Colonic Hypermobility in Water Avoidance Stress Rats by Activating the Nrf2 Signaling Pathway.

Irritable bowel syndrome (IBS) is an intestinal disorder, whose symptoms can be alleviated by certain dietary phytochemicals. This study explores the role and potential mechanisms of a natural flavonoid luteolin (LUT) in alleviating the excessive motility of colonic smooth muscles and reducing oxidative stress in IBS with diarrhea (IBS-D) rats. LUT reduces excessive intestinal motility and lowers reactive oxygen species (ROS) levels in a water avoidance stress (WAS) rat model. Moreover, LUT increases the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), activates the nuclear translocation of Nrf2, and greatly reduces the hydrogen peroxide (H2 O2 )-induced oxidative damage in intestinal epithelial cells. LUT, a phyto-active component, protects against excessive intestinal motility and diarrhea by regulating the Nrf2 signaling pathway and effectively reduces oxidative stress damage in the colon.

Comparison of the effects of moxibustion and acupuncture of combined "Biao-Ben" acupoints on intestinal sensitivity and autonomic nervous system function in rats with diarrhea-predominant irritable bowel syndrome.

To compare the effects of moxibustion and acupuncture of combined "Biao-Ben" acupoints (Biao indicates pathogenic factors of disease, Ben refers to body constitution) on a rat model of irritable bowel syndrome with diarrhea (IBS-D). Forty female SD rats were randomly divided into 4 groups：normal group, model group, moxibustion group, and acupuncture group, with 10 rats in each group. The IBS-D rat model was established by administering acute-chronic stress combined with folium sennae gavage for 28 days. Rats in the moxibustion group received moxibustion at bilateral "Zusanli"(ST36), "Guanyuan"(CV4), and "Neiguan"(PC6), while those in the acupuncture group received acupuncture at the same acupoints, both for 15 min every time, once a day. The treatments were administered for 21 days. The loose stool rate was observed. Colonic pain threshold and colonic distension threshold were measured by a self-made balloon catheter. Total distance traveled and grid crossing numbers were observed by open field test. Heart rate variability(HRV) time domain indexes SDANN and PNN50 were acguired by using electrophysiological recorder. Histopathological changes in the colon tissue were observed after HE staining. Contents of interleukin-6(IL-6), IL-8, and tumor necrosis factor-alpha(TNF-α) in serum were detected by ELISA. Compared with the normal group, rats in the model group showed increased loose stool rate(P<0.05), decreased pain threshold and distension threshold(P<0.05), reduced total distance traveled and grid crossing numbers in the open field test(P<0.05), decreased HRV time domain indexes SDANN and PNN50(P<0.01, P<0.05), and elevated levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the model group, the moxibustion group and acupuncture group showed decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50 (P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the acupuncture group, the moxibustion group showed further decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50(P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). No significant pathological changes were observed in the colon tissue of rats in each group. Moxibustion of combined "Biao-Ben" acupoints is more effective in regulating HRV and serum IL-6, IL-8, and TNF-α contents in the IBS-D rat model. Based on the combined "Biao-Ben" acupoints method, moxibustion has better therapeutic effects on IBS-D than acupuncture.

Modification of bile acids metabolism with multi-strain probiotic in patients with diarrhea predominant irritable bowel syndrome: a randomized study

one of the irritable bowel syndrome with diarrhea (IBS-D) mechanisms of development isbile acids (BA) malabsorption (BAM). The promising new therapeutic approach for BAM – probiotic&#x0D; bacteria producing bile salt hydrolase (BSH). The aim of the study was to compare the effect of multi-strain probiotic and cholestyramine combination with cholestyramine monotherapy on modifying the&#x0D; parameters of BA metabolism in IBS-D patients. Materials and methods. The trial was conducted asa randomized, open, parallel study and included 108 patients with IBS-D divided into 2 groups: casegroup (n=57) that received combination of probiotic (L. rhamnosus, L. plantarum, S. thermophilus, L.acidophilus, B. bifidum, B. longum, B. infantis, S. boulardii) with cholestyramine, and control group(n=51) that received cholestyramine monotherapy during 12 weeks. The total relative activity (RA)of gut bacterial BSH, serum BA (sBA) and fecal BA (fBA) were assessed in all patients. Results: total,&#x0D; primary and secondary sBA and fBA, proportions of primary and secondary fBA were significantly dif-ferent after 12 weeks within each group comparing to baseline, p&lt;0.05. In case group the proportions of&#x0D; primary and secondary sBA, RA of gut bacterial BSH were significantly different after 12 weeks compar-ing to baseline, p&lt;0.05. All the parameters of BA metabolism except absolute levels of secondary sBA&#x0D; were significantly different after 12 weeks between the control and case groups, p&lt;0.05. Conclusions:&#x0D; combination of cholestyramine and multi-strain probiotic led to more pronounced alterations of BA me-tabolism and increasing of gut bacterial BSH-activity comparing to cholestyramine monotherapy. It may&#x0D; explain possible mechanism of action of probiotics in patients with IBS-D and assumed BAM.

Genotyping of cryptosporidium species in cases of irritable bowel syndrome: A case control study from a tertiary care center

Irritable bowel syndrome (IBS) is functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of detectable structural abnormalities. Protozoan cysts are commonly found in the stool samples of patients with IBS and a rising body of evidence suggests a direct causal relationship. Cryptosporidium infection can be a potential candidate for IBS. We studied prevalence, association, and genotype of cryptosporidium at a tertiary care centre. Using a case-control design, a total of 100 cases and 100 controls were selected between 2016 and 2017. Fresh stool samples were collected and processed for microscopic examination. Positive samples were subjected to PCR RFLP for speciation and results analysed for Odd’s ratio, relative risk and relationship between variables. There was a high male preponderance (m: f=9:1). Most patients belonged to the middle age group (34.8-42.4 years). Amongst the clinical subtype IBS with diarrhoea (IBS-D) was the most common subtype (63%). Odd’s ratio for having IBS was 57.5 with cryptosporidium with a relative risk of 2.09. Adjusted Odd’s ratio for age was 1.014 suggesting a linear correlation (r value=0.07) with age. Our study shows a significant risk of developing IBS with cryptosporidium infection. The authors recommend studies with larger population samples both within the northern regions of India and across the country to determine prevalence, speciation of cryptosporidium and its relationship to IBS.

Cognition of abdominal pain and abdominal discomfort in Chinese patients with irritable bowel syndrome with diarrhea

BackgroundIn Asia, the proportion of patients with irritable bowel syndrome (IBS) with abdominal discomfort alone is significantly higher than that in western countries. The purposes of this study are to understand the cognition of abdominal pain and abdominal discomfort in Chinese patients with IBS and to compare the clinical characteristics of patients with abdominal pain alone and with abdominal discomfort alone.MethodsPatients with IBS with diarrhea (IBS-D) who met the Rome III diagnostic criteria and had episodes of at least one day/week were consecutively enrolled. The cognition of abdominal pain and abdominal discomfort were investigated through face-to-face unstructured interview. Patients were divided into a pain group and a discomfort group according to the cognition interviews, then the characteristics and severity of symptoms (IBS symptom severity scale, IBS-SSS), IBS quality of life (IBS-QOL) and psychological state were compared between groups.ResultsA total of 88 patients with IBS-D were enrolled. Most of the patients with self-reported abdominal pain described their pain as spasm/cramping; patients with self-reported abdominal discomfort had as many as 24 different descriptions of discomfort. Most patients having abdominal pain and discomfort could accurately distinguish the two symptoms. The degree of abdominal pain in the pain group was higher than abdominal discomfort in the discomfort group (P = 0.002). There was no significant difference in IBS-SSS, extra-intestinal pain, IBS-QOL, and psychological state between the two groups.ConclusionsFor Chinese patients with IBS-D, abdominal pain and abdominal discomfort are two different symptoms, but they have similar clinical features.Trial registrationChiCTR, ChiCTR1900028082. Registered 11 December 2019 - Retrospectively registered, http://www.chictr.org.cn.

Vitamin D Deficiency (VDD) and Benefits of Supplementation in Veterans with IBS-D.

Many veterans deployed to Gulf War areas suffer from persistent chronic diarrhea that is disabling and affects their quality of life. The causes for this condition have eluded investigators until recently and recent literature has shed light on the effect of vitamin D on the brain-gut axis. This study focused on determining clinical causes contributing to diarrhea and assessed whether reversing the identified causes, specifically vitamin D deficiency (VDD), could reduce the incidence of diarrhea in Gulf War veterans (GWVs). All patients completed a workup that included serologies (IBD, celiac), routine laboratory tests (CBC, chemistry panels, TSH, T4, CRP), cultures for enteric pathogens (C diff, bacteria, viruses, small intestinal bacterial overgrowth (SIBO)), and upper and lower endoscopies with histology and a trial of cholestyramine to exclude choleretic diarrhea and rifaximin for dysbiosis. A total of 4221 veterans were screened for chronic diarrhea, yielding 105 GWVs, of which 69 GWVs had irritable bowel syndrome with diarrhea (IBS-D). Paired t-tests demonstrated that all GWVs had VDD (t-11.62, df68 and sig(2-tailed) 0.0001) (defined as a vitamin D level less than 30 ng/mL with normal ranges of 30-100 ng/mL) but no positive serologies, inflammatory markers, abnormal endoscopies, cultures, or histology to explain their persistent diarrhea. There was no correlation with age, BMI, or inflammation. Some zip codes had a higher frequency of GWVs with VDD, but the number of deployments had no impact. Treatment with vitamin D supplementation (3000-5000 units), given in the morning, based on weight, reduced the number of bowel movements per day (p < 0.0001) without causing hypercalcemia. We suggest that VDD is important in the etiology of IBS-D in GWVs and that vitamin D supplementation significantly reduces diarrhea.

Medium-chain and long-chain fatty acids are associated with diarrheal predominant irritable bowel syndrome revealed by DESI-MSI.

Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders, but its pathogenesis remains unknown. Its development may be linked to intestinal dysmetabolism, directly and indirectly. The present study aimed to screen the differentially expressed small molecular substances in the mucosa of the colon between IBS with diarrhea (IBS-D) patients and healthy subjects and explore the pathogenesis of IBS-D. In this pilot study, the metabolites of colonic mucosa in ten patients with IBS-D and six healthy controls (HC) were analyzed by DESI-MSI. We also mapped the spatial distribution of the screened differential metabolites from samples of the IBS-D group and HC group. The results showed that 20 metabolites in the colonic mucosa of IBS-D were significantly more abundant, while the other 77 substances were significantly reduced. Enrichment analysis of 97 differential metabolites and KEGG pathway analysis revealed that six medium-chain and long-chain fatty acids were determined to be most overrepresented in the IBS-D group compared to the HC group. Four of these six fatty acids are all PUFAs. The DESI-MSI results suggested that these fatty acids were localized in the colonic mucosa and confirmed the differences in these fatty acids between IBS-D and HC. Medium-chain and long-chain fatty acids localized in the colonic mucosa are likely to be potential indicators for the differentiation of IBS-D from healthy subjects which may have implications in the mechanisms and possible preventive measures against IBS. ChiCTR2200060224.

Efficacy of bile salt hydrolase synthesizing probiotic bacteria in the treatment of irritable bowel syndrome with diarrhea

Background. One of the mechanisms of the of irritable bowel syndrome with diarrhea (IBS-D) is bile acid malabsorption (BAM). In addition to the use of bile acid sequestrants, probiotic bacteria synthesizing bile salt hydrolase (BSH) are promising in the treatment of probable BAM. The purpose of the study was to compare the effectiveness of combined treatment (a probiotic based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii and cholestyramine) with cholestyramine monotherapy in the treatment of IBS-D. Materials and methods. A 12-week randomized study included 108 patients with IBS-D divided into a control group (n = 51) receiving only cholestyra­mine and an experimental group (n = 57) receiving a combination of cholestyramine and the study probiotic. At baseline, the relative activity of BSH of the study probiotic capsules was determined. During the stages of the study, patients were examined using clinical scales. Results. The relative activity of BSH of the capsules with the studied probiotic was (2.07 ± 0.06) U/ml compared to (1.00 ± 0.04) U/ml of capsules with L.plantarum and (0.03 ± 0.01) U/ml — with L.plantarum without BSH genes. In the experimental group, the severity of bloating and visceral sensitivity index were lower after 8 and 12 weeks, and the value of the stool type according to the Bristol scale and its daily frequency — after 12 weeks compared to the control group, p &lt; 0.05. According to the scale of IBS-adequate relief, the percentage of achieving a clinical effect was higher in the experimental group compared to the controls after 12 weeks, odds ratio was 1.31 (95% confidence interval 1.03–1.68), p = 0.038. Conclusions. Additional prescription of a probiotic with BSH synthesizing bacterial strains is more effective in improving clinical manifestations of IBS-D and achieving a therapeutic effect compared to cholestyramine monotherapy.

Cannabidiol-Decorated Berberine-Loaded Microemulsions Improve IBS-D Therapy Through Ketogenic Diet-Induced Cannabidiol Receptors Overexpression.

Berberine (BR) shows promise as a candidate for treating irritable bowel syndrome with diarrhea (IBS-D). However, the undesired physicochemical properties and poor oral absorption limit its clinical translation. A ketogenic diet (KD) can induce intestinal overexpression of cannabidiol (CB) receptors, which may offer a potential target for IBS-D-specific delivery of BR. The microemulsions loaded with BR and decorated with cannabidiol (CBD/BR-MEs) were developed through a one-step emulsion method. The pharmaceutical behaviors of the CBD/BR-MEs were measured using dynamic light scattering and high-performance liquid chromatography. The efficacy of the anti-IBS-D therapy was evaluated by assessing fecal water content, Bristol score, and AWR score. The intestinal permeability were assessed through immunofluorescent staining of CB1 and ZO-1, respectively. The signaling of CREB/BDNF/c-Fos was also studied along with immunofluorescent and immunohistochemical examination of brain sections. The CBD/BR-MEs, which had a particle size of approximately 30 nm and a surface density of 2% (wt%) CBD, achieved greater than 80% (wt%) encapsulation efficiency of BR. The pharmacokinetics performance of CBD/BR-MEs was significantly improved in the KD-fed IBS-D rats than the standard diet-fed ones, which is highly related to intestinal expression of CB1 receptors. The treatment with CBD/BR-MEs and KD exhibited evident comprehensive advantages over the other groups in terms of anti-IBS-D efficacy. CBD/BR-MEs and KD synergistically decreased intestinal permeability. Moreover, the treatment with CBD/BR-MEs and KD not only blocked the CREB/BDNF/c-Fos signaling in the brain but also decreased the levels of neurotrophic factors, neurotransmitters, and inflammatory cytokines in the serum of IBS-D model rats. Such a design represents the first attempt at IBS-D-targeted drug delivery for improved oral absorption and efficacy through KD-induced target exposure, which holds promising potential for the treatment of IBS-D.