Constipation-predominant Irritable Bowel Syndrome Research Articles

Prevalence and Predictors of Functional Evacuation Disorder in Patients with Chronic Constipation

Abstract Background Functional evacuation disorder (FED) is the second most common cause of functional constipation (FC) after constipation-predominant irritable bowel syndrome. However, the data on FED is relatively scanty in our region. Hence, the present study was performed to evaluate the demographics of FED and to find out the predictors of FED in patients with chronic constipation. Methods A total of 134 patients with chronic constipation diagnosed according to the Rome IV criteria who were referred for high-resolution anorectal manometry (HRAM) were retrospectively enrolled in the present study. All FC patients who underwent HRAM were asked to fill a questionnaire and underwent anorectal manometry and were submitted to the balloon expulsion test (BET). Results The mean age of patients was 43.09 ± 9.32 years old, with a total of 76 (54%) males. The most common symptom was straining during defecation (87%) followed by incomplete evacuation (86%). The prevalence of FED, diagnosed by HRAM and by the BET was 39%. Patients with FED had a significantly higher percentage of straining and sensation of anorectal blockade compared with those without FED (96 versus 82%; p < 0.01; 81 versus 44%; p < 0.001, respectively). On the multivariate regression analysis, straining > 30 minutes (odds ratio [OR] = 3.63; p = 0.03), maximum squeeze pressure (OR = 1.05; p < 0.001), and balloon volume at maximal sensation (OR = 1.06; p < 0.001) were found to be significant independent predictors of FED. Conclusion Prolonged straining and sensation of anorectal blockade were significant indicators of FED in patients with chronic constipation.

Factors related to irritable bowel syndrome and differences among subtypes: A cross-sectional study in the UK Biobank.

Background: Irritable bowel syndrome (IBS) reduces patients’ quality of life and causes great burdens due to its unclear pathogenesis and criteria for diagnosis. This study aimed to explore the differences in prevalence and the influencing factors for IBS and its subtypes. Methods: The UK Biobank surveyed 174,771 adult participants who completed the Digestive Health Questionnaire (DHQ) through emails and websites. DHQ included the Rome III criteria, IBS symptom severity score, and Patient Health Questionnaire 12 Somatic Symptom score. The UK Biobank also asked regarding previous IBS diagnosis, diagnosis for post-infectious IBS (PI-IBS), and environmental exposures and associated conditions (including anxiety or depression, based on treatment sought or offered). Pearson’s Chi-squared test or Wilcoxon’s rank-sum test was used for potential associations. Binary logic regression based on sex stratification was used to examine associations between selected factors and IBS and its subtypes. Results: This study included 31,918 participants who met the Rome III criteria for IBS. The pooled prevalence of IBS in the UK Biobank was 18.3%, with mixed IBS as the predominant subtype (59.0%), followed by diarrhea-predominant IBS (25.1%), constipation-predominant IBS (14.7%), and untyped IBS (1.1%). IBS was significantly associated with somatization (male: OR = 5.326, 95% CI = 4.863–5.832; female: OR = 4.738, 95% CI = 4.498–4.992) and coeliac disease (male: OR = 4.107, 95% CI = 3.132–5.385; female: OR = 3.783, 95% CI = 3.310–4.323). Differences in antibiotics and mental status were presented among subtypes and sex. Furthermore, 1,787 individuals were diagnosed with PI-IBS in the group of patients with IBS. The prevalence of PI-IBS in IBS was 16.6% in the UK Biobank, and it was characterized by diarrhea, fever, bloody diarrhea, and vomiting. Conclusion: Somatization and coeliac disease are primary risk factors for IBS. Distinguishing differential risk factors is critical for the precise diagnosis and treatment of IBS subtypes, particularly sex-specific differences in mental health status. General practitioners should focus on the treatment according to IBS subtypes.

Effect of intracolonic volume on gastric sensory-motor responses in constipation-predominant irritable bowel syndrome.

Interaction between gut stimuli may induce symptom overlap in patients with functional gastrointestinal disorders. The aim is to determine the effect of increased volumes of colonic contents on gastric sensory/motor responses and satiety in patients with constipation-predominant irritable bowel syndrome (IBS-C) and overlapping dyspeptic symptoms, and a cohort of healthy subjects. In 15 patients with IBS-C and 10 healthy subjects, the effect of real versus sham colonic filling with gas (1080 ml) on gastric sensitivity (measured by stepwise distensions of the stomach), gastric compliance, abdominal perception, and nutrient drink tolerance was studied on separate days. In healthy subjects, colonic gas filling induced an increment in gastric sensitivity to distension (mean score 2.0 ± 0.2 before, and 3.0 ± 0.4 after; p=0.038). In IBS, basal sensitivity was greater and remained unchanged after colonic gas filling (score 4.0 ± 0.1 and 3.8 ± 0.3, respectively; p < 0.001 vs. basal in health). Colonic gas infusion induced abdominal symptoms that were significantly greater in IBS-C (score 2.6 ± 0.1) than in health (score 1.7 ± 0.4; p=0.027), with minor changes in gastric tone, and no changes in gastric compliance in both groups. Colonic filling produced a profound reduction in nutrient drink tolerance in IBS (791 ± 87 ml sham filling, 491 ± 58 ml gas filling; p < 0.001) but only a minor reduction in health (940 ± 70 ml sham filling, 860 ± 94 ml gas filling; p=0.223). The volume of the colonic contents modulates satiety in patients with IBS-C, due to a general visceral pan-hypersensitivity. These effects should be considered in the choice of treatment for constipation in these patients.

Effectiveness and Safety of Probiotics for Patients with Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials.

To perform a systematic review and meta-analysis to evaluate the effectiveness and safety of probiotics in the treatment of constipation-predominant irritable bowel syndrome (IBS-C), we searched for randomized controlled trials (RCTs) comparing probiotic care versus placebos for patients with IBS-C in five comprehensive databases (March 2022). The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.3 was used to perform a meta-analysis on stool consistency, abdominal pain, bloating, quality of life (QoL), fecal Bifidobacterium and Lactobacillus counts, and adverse events. The GRADE approach was used to evaluate the certainty of the evidence. Ten RCTs involving 757 patients were included. Only three studies were rated as having a low risk of bias. The meta-analysis results show that, compared to the placebo, probiotics significantly improved stool consistency (MD = 0.72, 95% CI (0.18, 1.26), p < 0.05, low quality) and increased the number of fecal Bifidobacteria (MD = 1.75, 95% CI (1.51, 2.00), p < 0.05, low quality) and Lactobacillus (MD = 1.69, 95% CI (1.48, 1.89), p < 0.05, low quality), while no significant differences were found in abdominal pain scores, bloating scores, QoL scores, or the incidence of adverse events (p > 0.05). The low-to-very low certainty evidence suggests that probiotics might improve the stool consistency of patients with IBS-C and increase the number of Bifidobacteria and Lactobacilli in feces with good safety. However, more high-quality studies with large samples are needed to verify the findings.

Efficacy of Newly Developed Kombucha-Based Specialized Food Product for Treatment of Constipation-Predominant Irritable Bowel Syndrome

ObjectivesAim: to assess the efficacy of kombucha-based specialized food product, enriched with inulin in patients with constipation-predominant irritable bowel syndrome.MethodsThe study (NCT05164861) was approved by LEC and enrolled subjects with constipation-predominant irritable bowel syndrome (according to ROME IV). The subjects were randomized to receive either 220 ml of a non-alcoholic drink, based on pasteurized kombucha (KG), enriched with inulin (1.15 g/100ml) or 220 ml water (control group, CG), for 10 days. Except study product, subjects were advised to follow their usual diet. Standard examination included evaluation of stool frequency (bowel movements per day), stool form (with the Bristol stool scale) and evaluation of concomitant symptoms (abdominal pain/discomfort, abdominal fullness, bloating, and feeling of incomplete bowel emptying) with the use of 5-point Likert scale before (BL) and 10 days after the start of intervention (EOT).ResultsThe complete data of 40 subjects were available for the analysis. Significant increase of stool frequency was found at the EOT compared to BL in KG (n = 20), Mean ± SD: 0.60 ± 0.31 to 0.85 ± 0.19 times/day; p = 0.004, while there was no change in CG (n = 20): 0.63 ± 0.33 vs 0.72 ± 0.28, p > 0.05. Mean values of stool scale form increased in KG (2.95 ± 1.15 to 4.4 ± 0.97; p = 0.001), while remained unchanged in CG (2.94 ± 1.2 vs 3.4 ± 1.2, p = 0.6). Mean values of the Bristol stool scale in KG and CG differed significantly at EOT (p = 0.018). Significant decrease in mean values of incomplete bowel emptying feeling was found in KG (1.88 ± 0.78 at BL vs 1.41 ± 0.56 points at EOT, p = 0.015), but not in the control group. There was no difference in patient's reports for other symptoms between KG and CG.ConclusionsNew specialized kombucha-based drink enriched with inulin is well-tolerated and increases stool frequency and consistency in patients with constipation-predominant irritable bowel syndrome.Funding SourcesRussian Science Foundation (research grant # 19-76-30,014).

New Specialized Kombucha-Based Non-alcoholic Pasteurized Beverage Shows Favorable Profile of Short-Term Safety and Tolerability in Patients With Constipation.

ObjectivesKombucha is a globally known beverage, perceived as “healthy”. It may be a basis for the development of new specialized beverages to increase dietary fiber consumption. However, safety and tolerability of the kombucha-based beverages is poorly studied yet. Aim: to assess short-term safety and tolerability of new kombucha-based pasteurized specialized non-alcoholic beverage, enriched with inulin.MethodsThis study (NCT05164861) enrolled subjects with constipation-predominant irritable bowel syndrome (per ROME IV). The subjects were randomized to receive either 220 ml of the non-alcoholic kombucha-based pasteurized beverage (KG), enriched with inulin (1.15 g/100ml) or 220 ml water (control group, CG), for 10 days. Except study product, subjects were advised to follow their usual diet. Organoleptic evaluation of the beverage; assessment of symptoms (abdominal pain/discomfort, abdominal fullness, bloating, heartburn) with the use of 5-point Likert scale; blood chemistry and hematology were performed before (BL) and on the 10th day of study (EOT). Patients were asked to report any adverse events during the study period.ResultsThere were 20 subjects in KG and 20 in CG groups. New specialized food product was well-tolerated, no SAE occurred during the study. No exacerbation of the pre-existing symptoms was observed in KG, including abdominal pain/discomfort (1.28 ± 0.56 vs 1.25 ± 0.56; p > 0.05), abdominal fullness (1.53 ± 0.69 vs 1.22 ± 0.47; p > 0.05), bloating (1.60 ± 0.64 vs 1.37 ± 0.60; p > 0.05), and heartburn (1.28 ± 0.62 vs 1.25 ± 0.52; p > 0.05) during the study. The rate of AEs was low (5%) and did not differ compared to CG. Mean integrative score of organoleptic evaluation of the beverage was good (91.0 ± 13.7%) with non-significant increase at EOT (94.2 ± 6.5%). No laboratory AE were observed.ConclusionsThis study suggest that new specialized kombucha-based drink enriched with inulin is well-tolerated, and has favorable safety profile.Funding SourcesRussian Science Foundation (research grant # 19-76-30,014).

Differential mRNA expression in ileal and colonic biopsies in irritable bowel syndrome with diarrhea or constipation.

Altered mucosal functions are documented in jejunal or colorectal mucosa from patients with irritable bowel syndrome (IBS). Our aim was to quantify ileal, ascending, and rectosigmoid colon mucosal expression of genes in IBS-diarrhea (D) and IBS-constipation (C). Forty-four patients with IBS-D, 30 with IBS-C, and 30 healthy volunteers underwent colonoscopic ileal, ascending, and rectosigmoid colon biopsies. Biopsies were stored in RNAlater at -80 °C, purified with on-column DNase, cDNA libraries prepared from 100-200 ng of total RNA, sequenced on Illumina NovaSeq 6000, and analyzed on Illumina's RTA version 3.4.4. Normalized mRNA expression was obtained using MAP-RSeq bioinformatics pipeline. Differential expressions in the groups (Log2-fold change) were measured using the bioinformatics package edgeR 2.6.2, corrected for false discovery rate (PADJ <0.05). There were 30 females with IBS-C and 31 females and 13 males with IBS-D. In IBS-D and IBS-C groups, there were differential expressions of 181 genes in ascending colon and 199 genes in rectosigmoid colon. The majority were gene upregulations in IBS-D with functions reflecting activation of inflammation genes, TRPV1 (visceral hypersensitivity) and neurotransmitters/receptors (specifically purinergic, GABA, and cannabinoid). Although gene differential expressions in the ascending and rectosigmoid colon mucosa of the two groups were different, the diverse upregulated genes involved immune functions, receptors, transmitters, ion channels, and transporters. Conversely, there was reduced expression of PI15 and PI16 genes that inhibit proteases. In patients with IBS-D and IBS-C, differential expressions of genes related to immune, transmitter, nociceptive, protease inhibition, channel, and transporter functions suggest opportunities to reverse the pathobiology and treat patients with IBS.NEW & NOTEWORTHY This study compares gene expression in mucosa of the terminal ileum, right colon, and left colon in patients with diarrhea- or constipation-predominant irritable bowel syndrome (IBS) and contrasts expression between these two disease entities and also between each entity and mucosa from healthy controls. The study shows there is differential expression of genes related to immune, transmitter, nociceptive, ion channel, and transporter functions, as well as reduced serine protease inhibition, in patients with IBS.

Magnetic resonance imaging assessed enteric motility and luminal content analysis in patients with severe bloating and visible distension.

Gastrointestinal symptoms in functional gut disorders occur without any discernible structural gut abnormality. Preliminary observations on enteric MRI suggest possible abnormal content and motility of the terminal ileum (TI) in constipation-predominant IBS (IBS-C) with severe bloating, and in functional bloating and distension (FABD) patients. We investigated whether MRI can quantify differences in small bowel (SB) content and motility between patients and healthy controls (HCs). 11 IBS-C (mean age 40 [21-52] years; 10 women) and 7 FABD (36 [21-56]; all women) patients with bloating and 20 HCs (28 [22-48]; 6 women) underwent enteric MRI, including dynamic motility and anatomical sequences. Three texture analysis (TA) parameters assessed the homogeneity of the luminal content, with ratios calculated between the TI and (1) the SB and (2) the ascending colon. Four TI motility metrics were derived. Ascending colon diameter (ACD) was measured. A comparison between HCs and patients was performed independently for: (1) three TA parameters, (2) four TI motility metrics, and (3) ACD. Compared with HCs, patients had TI:colon ratios higher for TA contrast (p<0.001), decreased TI motility (lower mean motility [p=0.04], spatial motility variation [p=0.03], and area of motile TI [p=0.03]), and increased ACD (p=0.001). IBS-C and FABD patients show reduced TI motility and differences in luminal content compared with HCs. This potentially indicates reflux of colonic contents or delayed clearance of the TI, which alongside increased ACD may contribute to symptoms of constipation and bloating.

Pharmacokinetics of DA-6886, A New 5-HT4 Receptor Agonist, in Rats.

DA-6886 is a novel serotonin (5-hydroxytrypamine [5-HT]) receptor 4 agonist for the potential treatment of constipation-predominant irritable bowel syndrome. The purpose of this study was to validate the quantitative assay of DA-6886 in rat plasma and to evaluate the pharmacokinetics and tissue distribution of DA-6886 in rats. The liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the robust quantification of DA-6886 in rat plasma was successfully validated and applied to the pharmacokinetic studies in rats. The pharmacokinetic parameters of DA-6886 in rats were evaluated following single intravenous or oral administration at three dose levels (2, 10, and 20 mg/kg). DA-6886 exhibited a smaller dose-normalized area under the plasma concentration–time curve (AUC) values and faster clearances in the low-dose group than in the high-dose group following both intravenous and oral administration. The steady-state volume of distribution (Vss) of DA-6886 was relatively large (4.91–7.84 L/kg), which was consistent with its high distribution to the liver, kidney, lung, and digestive tract, and was dose-independent. After oral administration, the extent of absolute bioavailability (F) tended to increase (18.9–55.0%) with an increasing dose. The slope of the log-transformed AUC and/or Cmax values versus log dose was greater than unity and greater for oral administration (~1.9) than for intravenous administration (~1.1). Because the nonlinear pharmacokinetics of DA-6886 was more obviously observed after oral administration, it appears that the saturation of pre-systemic intestinal and/or hepatic first-pass extraction of DA-6886 at high doses occurred.

A243 HISTAMINE H1-RECEPTOR ANTAGONISTS SUPPRESS THE HYPEREXCITABILITY OF NOCICEPTIVE NEURONS EXPOSED TO IBS-C PATIENT STOOL SUPERNATANTS

Abstract Background Abdominal pain is the primary cause of morbidity in many chronic GI disorders such as IBS, but the molecular mechanisms contributing to pain signaling are unclear. Stool supernatants from patients with diarrhea-predominant IBS increase the excitability of DRG neurons compared to supernatants from healthy controls, suggesting that mediators in the stool may sensitize nociceptors. Additionally, histamine has been implicated as a mediator of hypersensitivity in IBS patients. However, it is unclear if stool supernatants from constipation-predominant IBS (IBS-C) patients affect the excitability of DRG neurons. Furthermore, it is unknown if specific neuro-mediators in stool such as histamine impact the excitability of nociceptive neurons in this subgroup of IBS patients. Aims To evaluate whether IBS-C stool supernatants induce nociceptive signaling in DRG neurons compared to healthy control (HC) stool supernatants. If so, to evaluate the role of histamine 1 (H1) receptors in DRG neuron nociceptive signaling initiated by mediators in IBS-C stool supernatants. Methods IBS-C (n=5) and HC (n=2) patient stool was collected, filtered, and dissolved with Krebs solution in a 1:8 (g/v) dilution. Dorsal root ganglion (DRG) neurons from C57BL/6 mice were incubated with HC or IBS-C stool supernatant for 30 minutes. To evaluate whether histamine in stool supernatants can sensitize H1 receptors on nociceptors, DRG neurons were pre-incubated with the H1-receptor antagonist pyrilamine (1μM, 30 min) before stool supernatants. Changes in DRG neuronal excitability were recorded using perforated patch-clamp techniques to measure the rheobase (minimum input current needed to elicit an action potential) and the resting membrane potential (RMP). Results In neurons incubated with IBS-C stool supernatants (n=28) the rheobase decreased (63%) compared to healthy controls (78 ± 13.7 pA; n=6). This effect was reversed in DRG neurons pre-incubated with the H1 receptor antagonist, pyrilamine, (n=26) (77 ± 5.9 pA, p&amp;lt;0.001) compared to neurons incubated with IBS-C supernatant alone (50 ± 5.13 pA; n=28). No changes were found in the RMP. The data were analyzed with the non-parametric Kruskal-Wallis test. Conclusions IBS-C stool supernatants increase the excitability of DRG neurons compared to HC. Furthermore, the H1-receptor antagonist pyrilamine inhibits the neuronal hyperexcitability evoked by mediators in IBS-C patient stool. These findings suggest that the neuroactive metabolite histamine may contribute to visceral pain experienced by patients with IBS-C. Further studies are needed to examine whether similar signaling to nociceptive neurons by stool supernatants occurs in other subtypes of IBS. Funding Agencies CAG, CIHR

Relationship Between Systemic Immune-Inflammation Index and Irritable Bowel Syndrome

Irritable bowel syndrome is accepted as a functional disorder; however, there is growing evidence in favor of the inflammatory process contributing to its pathogenesis. We aimed to evaluate the role of the systemic immune-inflammation index as a marker of inflammation in patients with irritable bowel syndrome.The study was conducted in the outpatient clinic of the Gastroenterology Department with patients having constipationpredominant irritable bowel syndrome diagnosis according to Rome IV criteria between March 1, 2019 and December 31, 2020. The systemic immune-inflammation index was calculated and compared with age- and sex-matched healthy controls.The study was performed with 214 participants, 107 patients and 107 control groups. Platelet and neutrophil counts (P < .001, for both) were higher, and lymphocyte count (P = .003) was lower in the irritable bowel syndrome group. The systemic immune-inflammation index was higher in irritable bowel syndrome patients (P < .001). Multivariate logistic regression analyses showed the role of the systemic immune-inflammation index as an independent predictor of the presence of IBS (odds ratio: 1.100, P < .001).Systemic immune-inflammation index may be a cheap, universal, and reliable indicator of the inflammatory process in irritable bowel syndrome patients.

Clinical assessment and cytokines level in constipation-predominant irritable bowel syndrome participants treated with Lactobacillus-containing cultured milk drink.

Gut dysbiosis is linked with the pathophysiology of irritable bowel syndrome (IBS). Manipulation of intestinal microbiota using cultured milk drinks may stimulate the immune system, hence providing beneficial support in IBS treatment. This study aimed to investigate the effects of cultured milk drink on clinical symptoms, intestinal transit time (ITT), fecal pH and cytokines in constipation-predominant IBS (IBS-C) as compared to non-IBS participants. Each recruited participant was given three bottles of 125 ml cultured milk drink containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 consumed daily for 30 days. At pre- and post-30-day consumption, fecal pH, ITT, clinical symptoms, IL-6, IL-8 and TNF-α levels were assessed. Seventy-seven IBS-C and 88 non-IBS were enrolled. Post-consumption, 97.4% of IBS-C experienced improvements in constipation-related symptoms supported by the significant reduction of ITT and decreased fecal pH (p<0.05). All pro-inflammatory cytokines were significantly lower in post as compared to pre-consumption of cultured milk drinks in IBS-C (p<0.05). There was significant reduction in the IL-8 and TNF-α levels in post- as compared to pre-consumption for the non-IBS (p<0.05). Cultured milk drink taken daily improved clinical symptoms and reduced cytokines, hence should be considered as an adjunctive treatment in IBS-C individuals.

Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.

Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children. Mucosal biopsies were obtained from subjects aged 6 months to 18 years during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (<24 months, 24 months to <6 years, 6 to <12 years, and 12 to <18 years) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses. Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples. Uniform levels of GC-C mRNA expression were detected in children aged >6 months in the duodenum and >12 months in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children.

Small Intestinal Bacterial Overgrowth In Various Functional Gastrointestinal Disorders: A Case-Control Study.

Small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), but its' association with other functional gastrointestinal disorders (FGIDs) is less certain. This study aimed to explore SIBO in a multi-racial Asian population with various FGIDs compared to non-FGID controls. Consecutive Asian adults with Rome III diagnosed common FGIDs (functional dyspepsia/FD, IBS and functional constipation/FC) and non-FGID controls were subjected to glucose breath testing, with hydrogen (H2) and methane (CH4) levels determined. A total of 244 participants (FGIDs n = 186, controls n = 58, median age 45years, males 36%, Malay ethnicity 76%) were recruited. FGIDs had a higher prevalence trend of SIBO compared to controls (16% FGIDs vs. 10% controls, p = 0.278) with 14% in FD, 18% in IBS and 17% in FC. Compared to controls, SIBO was associated with diarrhoea-predominant IBS (IBS-D) (24% vs. 10%, P = 0.050) but not with other types of FGIDs. IBS-D remained an independent predictor of SIBO (OR = 2.864, 95% CI 1.160-7.071, p = 0.023) but not PPI usage nor history of diabetes (both p > 0.050) at multivariate analysis. Compared to controls, SIBO in IBS-D was associated with an elevated H2 level (≥ 20ppm from baseline) (18% vs. 3%, p = 0.017), but not CH4 levels (≥ 10ppm) (9% vs. 7%, p = 0.493). In addition, no difference was found in the prevalence of methane-positive SIBO between chronic constipation (constipation-predominant IBS and FC) compared to controls (9% vs. 7%, P = 0.466). SIBO is prevalent amongst multi-ethnic Asian adults with and without FGIDs. Amongst various FGIDs, only IBS-D is significantly associated with SIBO.

Use of Rifaximin in Irritable Bowel Syndrome Treatment

Introduction and purpose of the work: Irritable Bowel Syndrome (IBS) affects up to 10% of the population. The deterioration in health-related quality of life in IBS patients has been shown to be comparable to, and perhaps even more severe than, other serious chronic organic diseases such as inflammatory bowel disease, diabetes, hypertension, and end-stage renal disease. The aim of the study is to present a new method of IBS treatment.State of knowledge: There are four main types of IBS: Constipation-predominant IBS (IBS-C), Diarrhea-predominant IBS (IBS-D), Fluctuating IBS (IBS-M), and the unclassified form of IBS (IBS-U). Disturbances in entero-brain interactions play a key role in its multifactorial etiopathogenesis. In patients with IBS, quantitative and qualitative disturbances in the composition of the intestinal microbiota can be found. So far, it has not been possible to clearly establish the cause of the disease, so there is no possibility of causal therapy and effective cure. Both non-pharmacological methods and drugs, including rifaximin α, have been used in IBS therapy.Summary: Rifaximin has a positive effect on the symptoms of IBS. In clinical trials conducted in patients with IBS, the use of rifaximin for 2 weeks was associated with a reduction in the severity of joint symptoms, bloating, abdominal pain and discomfort, and an improvement in stool consistency within 4 and 12 weeks, and did not increase the risk of side effects. In the forms: with predominant diarrhea, mixed and unclassified, in order to reduce the overall symptoms as well as reduce the severity of flatulence and / or diarrhea, a 14-day therapy with rifaximin α is recommended.

Frequency of Irritable Bowel Syndrome (IBS) and its Risk Factors among MBBS Students of Allama Iqbal Medical College, Lahore

Background: Currently, there is a growing concern towards epidemiological and clinical research on functional gastrointestinal disorders. Irritable Bowel Syndrome is defined as a functional gastrointestinal disorder characterized by abdominal discomfort, abdominal pain, and altered bowel movements. It is the most common gastrointestinal disorder. It can be diarrhea-predominant IBS, constipation-predominant IBS, and mixed type IBS. Objective: The objective of this study was to determine the frequency of IBS among medical students of Allama Iqbal Medical College and to determine conditions and lifestyle habits that may act as significant risk factors for developing IBS. Methods: A cross-sectional study was conducted for over 5 months. A sample of 323 individuals was studied whereas the sampled individuals were selected using a "stratified random sampling technique". The study was conducted by collecting data through an online questionnaire during the global COVID pandemic. The questionnaire consisted of three parts. The first section consisted of demographic information, the second section consisted of a standard questionnaire determining the risk factors of IBS i.e., personal food and lifestyle habits, and the last section was aimed at determining whether the person was a case of IBS or not using the widely accepted and used “Rome III Criteria” and determining the predominant pattern of IBS. Results: The frequency of IBS was found to be 15.5%. Analysis of collected data revealed that the predictors for IBS were stress and reduced hours of daily sleep. It was also observed that a positive family history of irritable bowel syndrome predisposed the development of IBS in a person. 30% of subjects with a positive family history of IBS had symptoms suggestive of IBS. Conclusion: The study concludes that there is a high incidence of IBS among medical students because they live under higher stress conditions, concerning their academics and professional duty than students and professionals from other educational fields. Keywords: Irritable bowel syndrome, abdominal pain, stress, food consumption.

Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation.

BackgroundAbdominal pain and constipation are 2 main symptoms in patients with constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to investigate the effects and possible mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) in patients with IBS-C.MethodsForty-two patients with IBS-C were randomized into a 4-week sham-taVNS or taVNS treatment. The primary outcomes were complete spontaneous bowel movements per week (CSBMs/week) and visual analog scale (VAS) for abdominal pain. High-resolution anorectal manometry (HRAM) was performed to evaluate anorectal motor and sensory function. Cytokines and brain gut peptides were analyzed in blood samples. ECG was recorded for the assessment of autonomic function.ResultsCompared with sham-taVNS, (a) taVNS increased CSBMs/week (P = 0.001) and decreased VAS pain score (P = 0.001); (b) improved quality of life (P = 0.020) and decreased IBS symptom score (P = 0.001); (c) improved rectoanal inhibitory reflex (P = 0.014) and improved rectal sensation (P < 0.04); (d) decreased a number of proinflammatory cytokines and serotonin in circulation; and (e) enhanced vagal activity (P = 0.040). The vagal activity was weakly correlated with the CSBMs/week (r = 0.391; P = 0.010) and the VAS pain score (r = –0.347; P = 0.025).ConclusionsNoninvasive taVNS improves both constipation and abdominal pain in patients with IBS-C. The improvement in IBS-C symptoms might be attributed to the integrative effects of taVNS on intestinal functions mediated via the autoimmune mechanisms.Trial registrationwww.chictr.org.cn, no. ChiCTR2000029644.FundingNational Natural Science Foundation of China (grant no. 81970538 for FL).

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Baseline Predictors of Discontinuation of Prescription Drug Therapy for IBS-C: Cohort Analysis at an Integrated Healthcare System.

Effective prescription drug treatment of constipation-predominant irritable bowel syndrome (IBS-C) requires patients to remain on daily therapy, yet predictive factors to optimize treatment selection are unknown. We assessed whether common comorbidities including chronic overlapping pain conditions (COPCs), mood disorders, or concurrent medications influence the risk of discontinuing IBS-C prescription drug therapy. We included all IBS-C patients who initiated treatment with the secretagogues linaclotide or lubiprostone across the Michigan Medicine healthcare system between 2012 and 2016. A Cox proportional hazards model was constructed to model time-to-treatment discontinuation as a valid, quantifiable measure of IBS medication persistence using hazards ratios (HR) with 95% confidence intervals (CI). Our cohort included 225 patients on linaclotide and 492 on lubiprostone (mean age 48.3years, 86.9% women, 46.6% with at least one COPC, 60.3% with at least one mood disorder) with an average follow-up of 2.1years. Patients with at least one COPC (HR = 0.566; 95%CI = 0.371-0.863) and also women (HR = 0.535; 95%CI = 0.307-0.934) had a lower risk of discontinuing linaclotide, while COPCs predicted a trend toward increased discontinuation of lubiprostone (HR = 1.254; 95%CI = 0.997-1.576). Age, comorbid mood disorders, and baseline use of narcotics or benzodiazepines did not significantly mediate the risk of treatment discontinuation; our findings remained stable in univariate and multivariable analyses. COPCs and sex appear to influence the likelihood of discontinuation of two commonly prescribed secretagogues, while mood disorders, narcotics, and benzodiazepines may not. Routine assessment for comorbid COPCs prior to initiating therapy may optimize IBS-C treatment selection and outcomes in practice.

An evaluation of dietary adequacy among patients with constipation-predominant irritable bowel syndrome in Malaysia.

Background/AimsSubstantial proportions of patients with constipation-predominant irritable bowel syndrome (IBS-C) linked their symptoms with particular intake of foods. However, there is lack of current data regarding the intake among IBS-C patients before any dietary interventions. Thus, this study aimed to evaluate the dietary adequacy among IBS-C against the standard recommended nutrient intake (RNI) and healthy controls.MethodsA retrospective case-control study was conducted involving IBS-C patients and healthy control subjects. A validated 126-food items frequency questionnaire was administered to all the subjects to assess their dietary intake, guided by dietitians. The calculated nutrients intake for IBS-C patients was then compared against the standard RNI and healthy controls.ResultsA total of 306 subjects were recruited, among which 218 were diagnosed with IBS-C and 88 were included as healthy controls. IBS-C patients had significantly lower intake of wholegrain products, fried foods, dairy products, fruits, and vegetables compared to healthy controls. The daily intake of energy, certain macronutrients, and micronutrients among IBS-C patients was significantly lower than the healthy subjects. Less than 5% of IBS-C patients and healthy subjects achieved the standard recommendation for dietary fiber. Also, various vitamin intake (B1, B2, B6, folate, B12, E, K, and potassium) among IBS-C patients did not meet the standard RNI.ConclusionsDietary intakes of IBS-C patients did not meet the recommended intake for Malaysian and showed the nutritional inadequacies compared to the control subjects. Our study highlighted the importance of dietary evaluation prior to planning strategies for dietary intervention targeting IBS-C patients.