IBS-D Patients Research Articles

S822 Prevalence of Bile Acid Malabsorption in IBS-D Patients: Systematic Review and Meta-Analysis

S822 Prevalence of Bile Acid Malabsorption in IBS-D Patients: Systematic Review and Meta-Analysis

Multisample lipidomic profiles of irritable bowel syndrome and irritable bowel syndrome-like symptoms in patients with inflammatory bowel disease: new insight into the recognition of the same symptoms in different diseases.

Overlapping clinical manifestations of irritable bowel syndrome (IBS) and IBS-like symptoms in patients with inflammatory bowel disease (IBD-IBS) present challenges in diagnosis and management. Both conditions are associated with alterations in metabolites, but few studies have described the lipid profiles. Our aim was to pinpoint specific lipids that contribute to the pathogenesis of IBS and IBD-IBS by analyzing multiple biologic samples. Diarrhea-predominant IBS (IBS-D) patients (n = 39), ulcerative colitis in remission with IBS-like symptoms patients (UCR-IBS) (n = 21), and healthy volunteers (n = 35) were recruited. IBS-D patients meet the Rome IV diagnostic criteria, and UCR-IBS patients matched mayo scores ≤ two points and Rome IV diagnostic criteria. Serum, feces, and mucosa were collected for further analysis. Lipid extraction was carried out by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Lipidomics of mucosa and serum samples significantly differed among the three groups. Feces showed the most altered lipid species, and the enrichment analysis of 347 differentially abundant metabolites via KEGG pathway analysis revealed that alpha-linolenic acid metabolism was significantly altered in the two groups (P < 0.01). The ratio of omega-6/omega-3 fatty acid were imbalance in serum samples. This study revealed a comprehensive lipid composition pattern between IBS-D patients and UCR-IBS patients. We found several distinctive lipids involved in alpha-linolenic acid metabolism, reflecting an imbalance in the omega-6/omega-3 fatty acid ratio. Compared to mucosa and serum samples, fecal samples might have more advantages in lipidomics studies due to the convenience of sample collection and effectiveness in reflecting metabolic information.

Impaired Epithelial CD200L Tolerance Signaling in Irritable Bowel Syndrome Cases With Diarrhea May Be Associated With Recurrent Miscarriages.

There is a higher incidence of irritable bowel syndrome with miscarriages, and recurrent miscarriages of otherwise normal embryos have been linked to subnormal expression of the immune checkpoint inhibitor CD200L. We sought to determine if alterations in the expression of the CD200 immune checkpoint inhibitor occur in colonic tissue in IBS-D patients. Quantitative immunohistochemical staining of biopsies from proximal and distal colon or rectum for the inhibitory CD200L and CD200S molecules was done. CD56 cells were also enumerated as they play a role in recurrent miscarriages and may express CD200S. CD200L was decreased and CD200S was unchanged in epithelium but not stroma of 3 IBS-D cases. One case had an increase in both CD200L and CD200S. CD56 cells were also stained for CD200S. Degranulation was assessed by the percentage of extracellular CD200S that was increased as epithelial CD200L decreased. This pilot study was promising and warrants a larger sample to determine if a correlation between uterine implantation site CD200L and CD200S expression in normal and failing implantation sites is needed. Colonic epithelial CD200L may then provide useful information about the pathogenesis of the spontaneous miscarriage in individual cases.

Modified Gwakjeongtang for Diarrhea-Predominant Irritable Bowel Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Pilot Clinical Trial.

Irritable bowel syndrome (IBS) is a chronic condition characterized by recurrent abdominal pain associated with bowel movements. Modified Gwakjeongtang (MGT), an herbal prescription rooted in traditional East Asian medicine, consists of thirteen botanical drugs known for their potential to enhance intestinal barrier function, regulate gastrointestinal motility, and exhibit anti-inflammatory and antioxidant properties. Despite a few previous clinical trials highlighting MGT's potential for IBS symptom management, limited evidence exists with placebo control. In this pilot randomized clinical trial protocol, we aim to exploratively evaluate the efficacy and safety of MGT in patients with diarrhea-predominant IBS (IBS-D) by comparing it with a placebo. A total of 60 IBS-D patients will be enrolled, and eligible participants will be randomly allocated to either the MGT or placebo groups. Over a 4-week period, they will receive MGT or placebo granules three times a day. The primary endpoint will be the overall response rate post-treatment, determined through daily assessments of abdominal pain intensity and stool consistency. This clinical trial protocol has received approval from the Korean Ministry of Food and Drug Safety for an investigational new drug application and Institutional Review Board of the Kyung Hee University Korean Medicine Hospital. The research findings will be submitted and published in international peer-reviewed journal. Clinical research information service (registration number: KCT0008523).

Specific probiotics and prebiotics to improve the quality of life of patients with chronic irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic disorder with an important impact on patients' quality of life. Although several data indicate that psychological symptoms are frequently reported by patients with IBS, few therapies have been evaluated regarding these issues. A retrospective observational study was conducted to evaluate the effectiveness of a probiotic-based dietary supplement (Colicron®) in a group of patients with diarrhea-predominant IBS (IBS-D). We included patients treated with Colicron® (1 cps/day for 8 weeks). Primary endpoint was the gastrointestinal symptoms' remission evaluated by Visual Analogue Scale (VAS); secondary endpoint was the impact of the treatment on physical and mental health evaluated by Hospital Anxiety and Depression Score (HADS) and Short Form Health Survey 36 (SF-36). VAS was assessed at week 4 (T4), week 8 (T8) and week 12 (T12), whereas HADS and SF-36 were performed even at the start of the Colicron® treatment (T0). An improvement of VAS Score was observed at T8 (P<0.001) and T12 (P<0.05) compared to T4. Lower HADS-A (anxiety subdomain) score was obtained at each time point versus T0 (P<0.01), and higher scores of all SF-36 domains were observed during the treatment (0.05<P<0.001) compared to baseline. Moreover, HADS-D (depression subdomain) score, correlated positively, at T0 (P<0.05) and T4 (P<0.05) with the age, as well as a positive correlation was detected between disease duration (P<0.05) and age of patients (P<0.001). Colicron® could be useful in improving both gastrointestinal and psychological symptoms in IBS-D patients. Further prospective clinical trials are needed to confirm these preliminary data.

Fecal Microbial Composition and Predicted Functional Profile in Irritable Bowel Syndrome Differ between Subtypes and Geographical Locations.

Increasing evidence suggests a microbial pathogenesis in irritable bowel syndrome (IBS) but the relationship remains elusive. Fecal DNA samples from 120 patients with IBS, 82 Mexican (IBS-C: n = 33, IBS-D: n = 24, IBS-M: n = 25) and 38 British (IBS-C: n = 6, IBS-D: n = 27, IBS-M: n = 5), were available for analysis using 16S rRNA gene sequencing. Firmicutes (mean: 82.1%), Actinobacteria (10.2%), and Bacteroidetes (4.4%) were the most abundant taxa. The analysis of all samples (n = 120), and females (n = 94) only, showed no significant differences in bacterial microbiota, but the analysis of Mexican patients (n = 82) showed several differences in key taxa (e.g., Faecalibacterium) among the different IBS subtypes. In IBS-D there were significantly higher Bacteroidetes in British patients (n = 27) than in Mexican patients (n = 24), suggesting unique fecal microbiota signatures within the same IBS subtype. These differences in IBS-D were also observed at lower phylogenetic levels (e.g., higher Enterobacteriaceae and Streptococcus in Mexican patients) and were accompanied by differences in several alpha diversity metrics. Beta diversity was not different among IBS subtypes when using all samples, but the analysis of IBS-D patients revealed consistent differences between Mexican and British patients. This study suggests that fecal microbiota is different between IBS subtypes and also within each subtype depending on geographical location.

Integrated omics analysis reveals the epigenetic mechanism of visceral hypersensitivity in IBS-D.

Background and objective: IBS-D is a common functional bowel disease with complex etiology and without biomarker. The pathological and physiological basis of IBS-D focuses on visceral hypersensitivity. However, its epigenetic mechanism remains elusive. Our study aimed to integrate the relationship between differentially expressed miRNAs, mRNAs and proteins in IBS-D patients in order to reveal epigenetic mechanism of visceral hypersensitivity from transcription and protein levels and provide the molecular basis for discovering biomarkers of IBS-D. Methods: The intestinal biopsies from IBS-D patients and healthy volunteers were obtained for high-throughput sequencing of miRNAs and mRNAs. The differential miRNAs were selected and verified by q-PCR experiment followed by target mRNA prediction. Biological functions were respectively analyzed for target mRNAs, differential mRNAs and the previously identified differential proteins in order to explore the characteristic involved visceral hypersensitivity. At last, interaction analysis of miRNAs, mRNAs and proteins was performed for the epigenetic regulation mechanism from transcription and protein levels. Results: Thirty-three miRNAs were found to be differentially expressed in IBS-D and five of them were further confirmed, including upregulated hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p and downregulated hsa-miR-219a-5p, hsa-miR-19b-1-5p. In addition, 3,812 differential mRNAs were identified. Thirty intersecting molecules were found from the analysis on the target mRNAs of miRNAs and mRNAs. Fourteen intersecting molecules were obtained from the analysis on the target mRNAs and proteins, and thirty-six intersecting molecules were identified from analysis on the proteins and different mRNAs. According to the integrated analysis of miRNA-mRNA-protein, we noticed two new molecules COPS2 regulated by hsa-miR-19b-1-5p and MARCKS regulated by hsa-miR-641. Meanwhile some critical signaling pathways in IBS-D were found such as MAPK, GABAergic synapse, Glutamatergic synapse, and Adherens junction. Conclusion: The expressions of hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p, hsa-miR-219a-5p, and hsa-miR-19b-1-5p in the intestinal tissues of IBS-D patients were significantly different. Moreover, they could regulate a variety of molecules and signaling pathways, which were involved in the multifaceted and multilevel mechanism of visceral hypersensitivity of IBS-D.

A Tritordeum-Based Diet for Female Patients with Diarrhea-Predominant Irritable Bowel Syndrome: Effects on Abdominal Bloating and Psychological Symptoms.

Most female patients with irritable bowel syndrome (IBS) complain of abdominal bloating rather than abdominal pain and diarrhea. The higher incidence in women could be due to the so-called dysfunctional gas handling. Since diet seems the most effective and durable strategy for managing IBS symptoms, we aimed to evaluate the effects of a 12 week diet based on a relatively new cereal, Tritordeum (TBD), on gastrointestinal (GI) symptoms, anthropometric and bioelectrical impedance parameters, and psychological profiles in 18 diarrhea-predominant IBS (IBS-D) female patients with abdominal bloating as the dominant symptom. The IBS Severity Scoring System (IBS-SSS), the Symptom Checklist-90 Revised, the Italian version of the 36-Item Short-Form Health Survey, and the IBS-Quality of Life questionnaire were administered. The TBD reduces the IBS-SSS "Intensity of abdominal bloating" with a concomitant improvement in the anthropometric profile. No correlation was found between "Intensity of abdominal bloating" and "Abdominal circumference". Anxiety, depression, somatization, interpersonal sensitivity, and phobic and avoidance manifestations were significantly reduced after TBD. Lastly, anxiety was correlated with "Intensity of abdominal bloating". Overall, these results suggest the possibility of lowering abdominal bloating and improving the psychological profile of female IBS-D patients using a diet based on an alternative grain such as Tritordeum.

Changes in Tryptophan Metabolism on Serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome

(1) Background: L-tryptophan is a substrate for the synthesis of many biological compounds through the serotonin and kynurenine pathways. These compounds have a significant influence on gastrointestinal functions and mental processes. The aim of the study was to evaluate the urinary excretion of selected tryptophan metabolites in patients with constipation-predominant and diarrhoea-predominant irritable bowel syndrome (IBS-C and IBS-D, respectively), related to somatic and mental symptoms. (2) Methods: 120 people were included in the study and three groups were distinguished, with 40 individuals each, including healthy subjects (controls), patients with IBS-C and patients with IBS-D. The Gastrointestinal Symptoms Rating Scale (GSRS-IBS) was used to assess the severity of abdominal symptoms. The Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were used to evaluate the mental state of patients. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), L-tryptophan and the following metabolites in urine, related to the creatinine level, were measured: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA). (3) Results: In both groups of patients with IBS, changes in tryptophan metabolism were found as compared to the control group. We observed an increase in the activity of the serotonin pathway and a positive correlation between the 5-HIAA level and the GSRS score (p < 0.01) and HAM-A score (p < 0.001) in IBS-D patients. The IBS-C group was characterized by a higher concentration of kynurenines (KYN, QA) in urine. Moreover, the QA (p < 0.001) and KYNA (p < 0.05) levels were correlated with the HAM-D score among IBS-C patients. (4) Conclusions: Various changes in the tryptophan metabolism pathway can determine the differences in the clinical picture of irritable bowel syndrome. These results should be included in the nutritional and pharmacological treatment of this syndrome.

Could the Microbiota Be a Predictive Factor for the Clinical Response to Probiotic Supplementation in IBS-D? A Cohort Study.

Increasing evidence suggests the beneficial effects of probiotics in irritable bowel syndrome (IBS), but little is known about how they can impact the gut microbiota. Our objective was to evaluate the effects of a multistrain probiotic on IBS symptoms, gut permeability and gut microbiota in patients with diarrhoea-predominant IBS (IBS-D). Adults with IBS-D were enrolled in an open-label trial to receive a multistrain probiotic for 4 weeks. Abdominal pain, stool frequency, quality of life, gut permeability, and the luminal and adherent microbiota from colonic biopsies were evaluated before and after supplementation. Probiotics significantly improved symptoms and quality of life, despite having no impact on permeability in the global population. In the population stratified by the response, the diarrhoea responders displayed reduced colonic permeability after supplementation. The luminal and adherent microbiota were specifically altered depending on the patients' clinical responses regarding pain and diarrhoea. Interestingly, we identified a microbial signature in IBS-D patients that could predict a response or lack of response to supplementation. The multistrain probiotic improved the symptoms of IBS-D patients and induced distinct effects on the gut microbiota according to the patient's clinical response and initial microbiota composition. Our study further supports the need to develop individualised probiotic-based approaches regarding IBS.

Evaluation of efficacy and safety of Bacillus coagulans SNZ 1969 supplementation for irritable bowel syndrome: a randomized, double-blind, placebo-controlled study

Background: Probiotic potential (efficacy and safety) of Bacillus coagulans SNZ 1969 has been studied in patients with constipation-predominant irritable bowel syndrome (IBS-C) and-diarrhea predominant IBS (IBS-D).Methods: This randomized, double-blind, two-arm, placebo-controlled parallel study randomized 92 patients (1:1) to receive either 500 million CFU of Bacillus coagulans SNZ 1969 (treatment group) or placebo (placebo group) twice daily for 60 days under two subtypes of IBS, IBS-D (n=46) and IBS-C (n=46). Primary outcomes were changes in IBS symptom severity noted using the gastrointestinal symptom rating scale-IBS version (GSRS-IBS) on days 30, 60, and 75, and the number of treatment responders defined by subject’s global assessment (SGA) of relief ≤3 and ≤2 at days 30 and 60, respectively. We also assessed patient’s quality of life.Results: The GSRS-IBS scores reduced from day 30 through 75 in both IBS groups treated with Bacillus coagulans SNZ1969 compared to placebo (p&lt;0.05). Higher GSRS-IBS score was noted in patients with IBS-C in the treatment group (22.45±2.7) than the placebo group (3.55±3.02; p&lt;0.0001), and this trend was similar in IBS-D patients (p&lt;0.0001). Most patients (90%) with IBS-C and all with IBS-D responded to Bacillus coagulans SNZ 1969 compared to no responders with placebo (p&lt;0.0001). The SF-8 scores significantly reduced in patients receiving Bacillus coagulans SNZ 1969 than placebo for both IBS subtypes. One adverse event unrelated to the study treatments was reported in IBS-D group.Conclusions: Bacillus coagulans SNZ 1969 is safe, effective in alleviating IBS-associated clinical symptoms, and improves quality of life.

Baseline gut microbial profiles are associated with the efficacy of Bacillus subtilis and Enterococcus faecium in IBS-D

Objective Little is known about association between the efficacy of probiotics and baseline gut microbiota in irritable bowel syndrome (IBS). We aimed to explore gut microbiota in diarrhea-predominant IBS (IBS-D) and whether baseline gut microbiota was related to the efficacy of Bacillus subtilis and Enterococcus faecium (BE). Methods This study recruited 19 healthy controls (HC) and 50 IBS-D patients, among whom 19 patients were administrated 500 mg BE orally three times daily for 2 weeks. Clinical data and fecal samples were collected from patients before and after treatment. 16S rRNA sequencing was performed to obtain fecal bacterial data. Results There was no significant difference of alpha diversity, beta diversity, profiles of microbial phyla and genera between HC and IBS. BE improved IBS-SSS (IBS severity scoring system) and stool consistency, and altered Enterococcus, Blautia, Lachnoclostridium and Fusobacterium without significant impact on microbial structure in IBS-D. Notably, baseline fecal bacterial composition differed between non-responders and responders to BE concerning abdominal pain and bloating, with Atopobium, Pyramidobacter, Ruminococcus gnavus and Peptostreptococcus enriched in responders in terms of abdominal pain. There was reduced abundance of Prevotella, Ruminococcaceae UCG, Eubacterium eligens, Faecalibacterium and Eubacterium coprostanoligenes in responders compared with non-responders. Furthermore, BE increased beneficial bacteria including Faecalibacterium, Blautia and Butyricicoccus, decreased Lachnoclostridium and Bilophila, and influenced some microbial metabolic pathways in responders, such as mineral absorption, metabolism of arachidonic acid, d-arginine, D-ornithine, phenylalanine and vitamin B6. Conclusion Baseline fecal microbiome is associated with the efficacy of BE in attenuating abdominal pain and bloating in IBS-D.

The serotonin receptor 3E variant is a risk factor for female IBS-D

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.

Gut Microbiota Alter Visceral Pain Sensation and Inflammation via Modulation of Synthesis of Resolvin D1 in Colonic Tuft Cells.

Background and AimsVisceral hypersensitivity and low grade mucosal inflammation are frequently observed in a subpopulation of irritable bowel syndrome (IBS) patients. The responsible mechanism is unclear. Resolvins are a novel class of anti-inflammatory lipid mediators that regulate resolution of inflammation and pain. We hypothesize that resolvin D1 (RvD1) synthesis is reduced in IBS-D colonic mucosa and contribute to the development of visceral hypersensitivity. MethodsWe used ELISA and qPCR to quantify the levels of RvD1 synthesis and the gene expression of LOX5 and LOX12 in colonic biopsy samples from healthy individuals (HC) or IBS-D patients. To evaluate the role of gut bacteria in regulating RvD1 synthesis, we colonized germ-free mice with different strains of bacteria, fecal microbiota from HC individuals or IBS-D patients. To evaluate the role of tuft cells in RvD1 synthesis, we examined the effect of fecal supernatant of IBS-D or HC subjects on human colonoids as well as colonoids from mice in which Chat-cre recombinase vector was used to knock-in diphtheria toxin sensitive receptor (DTRf/f) or knock-out the expression of Tlr4f/f or MyD88f/f. ResultsWe report that colonic biopsy samples from IBS-D patients generated significantly lower level of RvD1 and LOX5 mRNA. The conventionalization of germ-free mice with microbiota from IBS-D patients or gram-negative bacteria inhibited RvD1 biosynthesis and caused visceral hypersensitivity and mucosal inflammation. Colonic organoid studies demonstrate that Lps downregulated Lox5 mRNA expression and synthesis of RvD1 via Tlr4-MyD88 receptor signaling pathway in colonic tuft cells. ConclusionsOur findings indicate that RvD1 is generated in colonic tuft cells to regulate gut sensitivity to mechanical stimulation. Colonic commensal bacterial composition regulates the synthesis of RvD1 in colonic mucosa which is reduced in IBS-D patients. This appears to be mediated by elevated fecal lipopolysaccharide secondary to gram-negative gut dysbiosis.

Distinctions Between Fecal and Intestinal Mucosal Microbiota in Subgroups of Irritable Bowel Syndrome.

Recent studies have shown that changes in the intestinal microbiota contribute to the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the characteristics of the fecal and intestinal mucosal microbiota in IBS patients, and the correlation between microbiota and clinical manifestations. Fecal and intestinal mucosal samples were collected from 14 constipation-predominant IBS (IBS-C) patients, 20 diarrhea-predominant IBS (IBS-D) patients, and 20 healthy controls (HCs). 16S rRNA gene sequencing and fluorescence in situ hybridization were used for the analysis of samples. Community richness and diversity of the fecal microbiota in IBS patients were significantly reduced compared with the HCs. The mucosal samples in IBS patients showed decreased Bifidobacterium and increased Bacteroides caccae compared with HCs; Eubacterium and Roseburia were decreased in IBS-C patients and increased in IBS-D patients. A comparison of the fecal and mucosal microbiota in IBS patients showed significantly increased Bifidobacterium in fecal samples and a decrease in mucosal samples in IBS-C patients; Bacteroides caccae and Roseburia were significantly reduced in fecal samples and increased in mucosal samples of IBS patients. A correlation between microbiota and clinical manifestations in IBS patients showed that Bacteroides caccae and Roseburia in fecal samples and Bifidobacterium and Eubacterium in mucosal samples were associated with abdominal pain and distention. Distinct differences exist between the fecal and intestinal mucosal microbiota in IBS patients, with the changes in the latter appearing more consistent with the pathophysiology of IBS. Changes in intestinal microbiota were associated with the clinical manifestations in IBS.

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.

Expression of TRP Channels in Colonic Mucosa of IBS-D Patients and Its Correlation with the Severity of the Disease.

Aim Lots of researches have endeavored to elucidate the pathogenetic mechanism of visceral hypersensitivity in order to guide the therapy of diarrhea predominant-irritable bowel syndrome (IBS-D). Transient receptor potential (TRP) channels and their role in visceral nociception have been vastly investigated. We investigated the expression of TRP channels in IBS-D colonic biopsies and its correlation with the severity of the disease. Methods Sigmoid biopsies were obtained from 34 IBS-D patients and 28 healthy controls (HCs). IBS-D was diagnosed according to Rome IV criteria. Their clinical parameters were assessed through questionnaires. Expression of TRPV1, TRPV4, TRPA1, TRPM2, and TRPM8 was evaluated with immunohistology staining. Results Expression levels of TRPV1, TRPV4, and TRPA1 in the colonic mucosa of IBS-D patients were significantly higher than those in HCs (p < 0.05), while there was no obvious difference of TRPM2 and TRPM8 expression between IBS-D patients and HCs. In addition, the expression levels of TRPV1 and TRPA1, but TRPV4, in the colonic mucosa correlated positively with the severity of diseases (r = 0.6303 and 0.4506, respectively, p < 0.05). Conclusions Expression of TRPV1, TRPA1, and TRPV4 in the colonic mucosa was enhanced in IBS-D patients compared with HCs with the former two correlated with the severity of the disease. TRP channels might be promising biomarkers in the diagnosis and estimate of the severity in IBS-D.

Golden bifid might improve diarrhea-predominant irritable bowel syndrome via microbiota modulation

ObjectiveGut microbiota might play a crucial role in the pathogenesis of irritable bowel syndrome (IBS), and probiotics supplement may be an effective treatment option. This study aims to explore the therapeutic effects of Golden bifid on the diarrhea-predominant IBS (IBS-D).MethodsTwenty-one consecutive IBS-D patients were recruited based on Rome IV criteria. All patients took 2000 mg Golden bifid triple daily for 4 weeks. Gastrointestinal (GI) symptoms, psychological symptoms, small intestine bacterial overgrowth (SIBO) and fecal microbiota characteristics were evaluated in IBS-D patients before and after treatment.ResultsAfter 4-week treatment of Golden bifid, the GI symptoms such as abdominal pain (2.90 ± 1.04 vs. 1.90 ± 1.26, P = 0.002), abdominal distension (2.00 ± 1.34 vs. 1.29 ± 1.31, P = 0.007), diarrhea (3.24 ± 1.37 vs. 1.81 ± 1.21, P = 0.001), defecatory urgency (3.48 ± 1.03 vs. 2.33 ± 1.35, P = 0.000) and incomplete evacuation (2.71 ± 1.15 vs. 1.76 ± 1.26, P = 0.003) were significantly alleviated in IBS-D patients. The Self-Rating Depression Scale (SDS) decreased significantly (46.19 ± 11.36 vs. 43.33 ± 9.65, P = 0.041), and SIBO could be eradicated in 25% (4/16) of IBS-D patients with SIBO. Meanwhile, the abundance of Unclassified Lachnospiraceae and Dorea in genus level and Unclassified Lachnospiraceae, Bacterium Dorea, Bacterium Butyricicoccus and Dorea formicigenerans ATCC 27755 in species level were increased in fecal microbiota (P < 0.05).ConclusionsGolden bifid could improve most of GI symptoms and depressive symptoms in IBS-D patients and eradicate a small proportion of SIBO in those IBS-D patients with SIBO. What's more, Golden bifid could also modulate the fecal microbiota in IBS-D patients, which implied that the Golden bifid might improve IBS-D via microbiota modulation.

Colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome.

There is growing evidence that eosinophilic infiltration can release mediators which are harmful to the intestinal epithelium in patients with irritable bowel syndrome (IBS). Although cyclooxygenase 2 (COX-2) and nuclear factor-kappa beta (NF-kB) expression had been previously reported to increase in many inflammatory conditions, there is a paucity in data investigating their expressions in IBS. Our aim was to evaluate colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome. A total of 80 patients who met the inclusion criteria of IBS based on Rome IV symptoms questionnaire were subjected to abdominal ultrasound, laboratory investigations, serum immunoglobulin E (IgE) level assessment and colonoscopic examination. Immunohistochemistry was performed to detect COX-2 and NF-kB expression in colonic biopsies obtained from IBS patients. Histopathological examination showed that 60 colonic biopsy specimens (75%) showed few mixed inflammatory cells ≤3 cells/ HPF, 12 biopsy specimens (15%) showed eosinophilic infiltration ≥25 eosinophils/HPF and 8 biopsy specimens (10%) showed severe lymphocytic infiltration and aggregation. Colonic eosinophilic infiltrate was significantly higher among patients presented with IBS-D subtype. Serum IgE was significantly higher among patients with colonic eosinophilic infiltrate than the others. In IBS-D patients, colonic mucosa showed positive expression of COX-2 and NF-kB in 52.1% and 81.25% of cases, respectively. Patients with IBS -particularly IBS-D subtype- should undergo colonoscopy and biopsy to exclude underlying inflammatory pathology. Moreover, patients with positive COX-2 and NF-kB need further evaluation and follow-up.

Quantitative Evaluation of Mucosal Mast Cells in the Colon in Patients with Irritable Bowel Syndrome

Background: Recent studies have shown that mast cells play an important role in the pathogenesis of irritable bowel syndrome as they release variable mediators which alter enteric nerve and smooth muscle function. The aim of this study was to determine whether mucosal mast cells were increased in the colonic mucosa of IBS patients compared to controls. Materials and Methods: This case-control study was conducted in the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during the period from April 2016 to March 2017 on cases of IBS and comparison group. We recruited 25 IBS patients and 25 healthy controls for this study. Colonoscopic biopsy was taken from the caecum, ascending colon, descending colon, and rectum. Tissue was stained with Giemsa, and then quantitative evaluation of mast cells was performed. Mast cells counts were compared between the two groups of patients. Results: Mast cells were significantly higher in the caecum, ascending colon, descending colon, and rectum in all subtypes of IBS patients compared to control (10.40±2.10, 6.76±1.83, 8.08±2.19, and 9.16±2.46 vs. 4.20±1.01, 3.32±0.69, 3.04±0.84, and 3.84±1.07 per HPF, respectively). Among four sites, mast cells were significantly higher in the caecum in IBS patients. Mucosal mast cells were relatively elevated in IBS-D patients compared to IBS-C and IBS-M patients, but this was not statistically significant. Conclusion: Mast cells were significantly increased in the caecum, ascending colon, descending colon, and rectum of the patients with IBS compared to controls. These findings suggest that mast cells may play an essential role in the pathogenesis of IBS. TAJ 2021; 34: No-2: 09-14