Polycystic Ovary Syndrome and Irritable Bowel Syndrome: Is There a Common Pathway?

OBJECTIVE: Little is known about how polycystic ovary syndrome (PCOS) is linked to irritable bowel syndrome (IBS). This study aimed to review the existing literature regarding the association between PCOS or its symptoms and complications with IBS. METHODS: In this review, studies that investigated the proposed cross-link between features of PCOS and IBS were included. This review collectively focused on recent findings on the mechanism and novel insight regarding the association between IBS and PCOS in future clinical practice. An electronic search of PubMed, Scopus, Epistemonikos, Cochrane Library and Google Scholar was performed. We did not restrict the study setting and publication date. RESULTS: The existing evidence has not completely answered the question of whether there is an association between PCOS and IBS and vice versa. Six case-control studies (793 women with PCOS and 547 women in the control group) directly assessed the association between PCOS and IBS. The prevalence of IBS among women with PCOS in these studies has ranged from 10% to 52% compared with 5%-50% in control groups. Evidence suggested the common pathways may have contributed to the interaction between IBS and PCOS, including metabolic syndrome, sex hormone fluctuation, dysregulation of neurotransmitters, psychological problems and environmental and lifestyle factors. To date, it is still ambiguous which of the mentioned components largely contributes to the pathogenesis of both. CONCLUSION: Although limited evidence has shown a higher prevalence of IBS in women with PCOS, there are several potential, direct and common indirect pathways contributing to the development of both IBS and PCOS.

Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7-17 years old with irritable bowel syndrome with constipation (IBS-C). METHODS: In this 4-week, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study, children with IBS-C were randomized to once-daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7-11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 1:1:1:1:1 allocation (the higher option of Doses A-C or 290 µg). The primary efficacy endpoint was a change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. RESULTS: Efficacy, safety, and tolerability were assessed in 101 patients. In the intent-to-treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment-emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. CONCLUSIONS: Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.

Mast Cell Activation Syndrome and Gut Dysfunction: Diagnosis and Management.

PURPOSE OF REVIEW: Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced by an individual. The diagnosis and treatment of MCAS with specific focus on gastrointestinal (GI) manifestations is reviewed. RECENT FINDINGS: Although biomarkers for MCAS remain elusive, testing for baseline serum tryptase will distinguish the type of mast cell disorder and urine tests for mast cell mediator metabolites may support the diagnosis. Endoscopy and Colonoscopy with biopsies is not used to diagnose MCAS but is important to rule out other conditions that may cause symptoms. There is increased awareness of the association between MCAS and autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which all impact GI symptoms. MCAS is a disorder often of unknown etiology (idiopathic) and characterized by intermittent allergy type symptoms that affect multiple organ systems after exposure to a trigger. GI symptoms including abdominal cramping and loose stool are prominent and mimic those of IBS. Diagnostic testing is performed to assess for elevations in mast cell mediators during symptoms and to rule out other conditions. A comprehensive treatment plan includes medications that target mast cells, treatments for associated conditions including autonomic dysfunction, and management of comorbid psychiatric illness and nutritional deficits.

The association between vitamin-D deficiency and fecal incontinence.

BACKGROUND: Vitamin-D is essential for musculoskeletal health. We aimed to determine whether patients with fecal incontinence (FI): (1) are more likely to have vitamin-D deficiency and, (2) have higher rates of comorbid medical conditions. METHODS: We examined 18- to 90-year-old subjects who had 25-hydroxy vitamin-D levels, and no vitamin-D supplementation within 3 months of testing, in a large, single-institutional electronic health records dataset, between 2017 and 2022. Cox proportional hazards survival analysis was used to assess association of vitamin-D deficiency on FI. KEY RESULTS: Of 100,111 unique individuals tested for serum 25-hydroxy vitamin-D, 1205 (1.2%) had an established diagnosis of FI. Most patients with FI were female (75.9% vs. 68.7%, p = 0.0255), Caucasian (66.3% vs. 52%, p = 0.0001), and older (64.2 vs. 53.8, p < 0.0001). Smoking (6.56% vs. 2.64%, p = 0.0001) and GI comorbidities, including constipation (44.9% vs. 9.17%, p = 0.0001), irritable bowel syndrome (20.91% vs. 3.72%, p = 0.0001), and diarrhea (28.55% vs. 5.2%, p = 0.0001) were more common among FI patients. Charlson Comorbidity Index score was significantly higher in patients with FI (5.5 vs. 2.7, p < 0.0001). Significantly higher proportions of patients with FI had vitamin-D deficiency (7.14% vs. 4.45%, p < 0.0001). Moreover, after propensity-score matching, rate of new FI diagnosis was higher in patients with vitamin-D deficiency; HR 1.9 (95% CI [1.14-3.15]), p = 0.0131. CONCLUSION & INFERENCES: Patients with FI had higher rates of vitamin-D deficiency along with increased overall morbidity. Future research is needed to determine whether increased rate of FI in patients with vitamin-D deficiency is related to frailty associated with increased medical morbidities.

Microscopic colitis found together with celiac disease in a female population is associated with one episode of lymphocytic colitis.

BACKGROUND: Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. METHODS: Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. RESULTS: MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020-17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042-1.506; p = 0.058). CONCLUSION: Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.

Relationship of migraine and other forms of chronic pain.

The disability of migraine, a highly prevalent condition, is worsened by a second comorbid chronic pain condition. There is evidence of a relationship between migraine and several visceral pain conditions including irritable bowel syndrome, endometriosis, and dysmenorrhoea, as well as nonvisceral conditions including temporomandibular dysfunction, fibromyalgia, and lower back pain. While the mechanisms linking these conditions are inadequately surmised, a two-way relationship between migraine and these comorbidities likely exists. The progression and chronification of migraine is associated with peripheral and central sensitization, which may predispose to other conditions. Conversely, aspects of the mechanism of each comorbid condition may promote further migraine attacks. This chapter introduces each comorbidity, briefly summarizes the existing evidence, and discusses implications for treatment.

Comparative characteristics of fatigue in irritable bowel syndrome and inflammatory bowel disease: A systematic review and meta-analysis.

OBJECTIVE: Fatigue is a common symptom in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to distinguish fatigue characteristics in IBS and IBD, two functional and organic disorders. METHODS: We systematically searched the PubMed and Cochrane Library databases from inception to June 30, 2023, and conducted a meta-analysis to generate precise estimates and 95% confidence intervals. The analyses were stratified by fatigue type, severity, sex, disease phase, and comorbidities, and study quality was assessed using Newcastle-Ottawa Scale (NOS). RESULTS: Our analysis included 74 data (13 IBS, 31 CD, 30 UC) encompassing 16,689 participants (6484 males, 7402 females, and 2803 unknown). Overall, fatigue prevalence trended higher in IBS (54.5% [95%CI, 44.5-64.6]), followed by CD (49.8% [95%CI, 44.0-55.5]) and UC (43.6% [95%CI, 38.5-48.7]). This pattern persisted across sub-analyses, including general fatigue (63.4% vs. 51.3% vs. 45.3%) and moderate to severe fatigue (73.8% vs. 59.5% vs. 52.7%) for IBS, CD, and UC, respectively. Female predominance was observed in all three diseases (odds ratio: 1.5 in IBS and CD, 1.8 in UC). Fatigue prevalence significantly varied between disease phases (active vs. remission) in CD (61.3% vs. 36.3%) and UC (53.8% vs. 32.6%). Anemia, anxiety/depression, and/or IBS-like symptoms also contributed to fatigue in CD and UC. CONCLUSIONS: This study is the first extensive comparison of fatigue prevalence and features in IBS, CD, and UC. The findings offer valuable insights for treatment and management, aiding our understanding of functional and organic diseases.

Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

OBJECTIVE: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

Evaluation of gallbladder contractility and Doppler findings in patients with irritable bowel syndrome; a case-control study.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder causing abdominal pain, altered bowel habits and bloating without structural issues. Gallbladder dysfunction may be linked to IBS due to disrupted cholecystokinin release. This study aims to assess gallbladder function and related hemodynamic parameters using Doppler ultrasound in IBS before and after meals. METHOD: In this case-control study, we investigated gallbladder function differences between constipation-predominant IBS (C-IBS) patients and healthy volunteers. Participants underwent ultrasonography to measure gallbladder parameters before and after consuming a predefined meal. Gallbladder volume, wall thickness and resistance index (RI) of cystic and superior mesenteric arteries (SMA) were assessed. Student t-test and paired t-test were used to compare case and control groups and pre- and post-meal data, respectively. RESULTS: A total of 34 people (18 C-IBS and 16 healthy control) were included. The mean (Standard deviation) of gallbladder fasting volume was measured 24.74 (8.85) and 29.73 (9.65) cubic millimeter for case and controls, respectively. Postprandial volume was 11.34 (5.66) and 16.9 (6.16) cubic millimeter for case and controls respectively. We observed a statistically significant difference in emptying fractions (EF) between groups (p value = 0.009). IBS patients had a smaller fasting SMA RI (p value = 0.016) but the fraction of change after meal was not significant (p value = 0.10). The cystic artery RI did not reach statistical significance between the fasting and post-meal values (p value = 0.067). CONCLUSION: IBS patients have a higher emptying fraction and lower change in SMA RI compared to healthy controls. Further studies with larger sample size, inclusion of patients with different coexisting conditions and subtypes of IBS and combining colon transit study with gallbladder ejection fraction evaluation can be used to further provide more meaning to this study.

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome: A study from China.

BACKGROUND: Functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) represent a spectrum of constipation disorders. However, the majority of previous clinical investigations have focused on Western populations, with limited data originating from China. AIM: To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population. METHODS: Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled. FC and IBS-C diagnoses were established using ROME IV criteria, and patients underwent high-resolution anorectal manometry (ARM) and a colonic transmit test using the Sitz marker study. Constipation-related symptoms were obtained through questionnaires. Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21. The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared. RESULTS: No significant differences in sex, age or abdominal discomfort symptoms were observed between IBS-C and FC patients (all P > 0.05). The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC (36.63% vs 15.91%, P < 0.05), while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group (50% vs 26.73%, P < 0.05). Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM. IBS-C patients were found to have a higher prevalence of depression than FC patients (66.30% vs 42.42%, P < 0.05). The scores for feelings of guilt, suicide, psychomotor agitation, diurnal variation, obsessive/compulsive disorder, hopelessness, self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients (P < 0.05). For IBS-C (χ2 = 5.438, P < 0.05) but not FC, patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time. For IBS-C patients but not FC patients, the threshold of first constant sensation, desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety (r = 0.414, r = 0.404, and r = 0.418, respectively, P < 0.05). The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression (69.6% vs 41.9%, χ2 = 4.054, P < 0.05). CONCLUSION: Our findings highlight both overlapping and distinctive patterns of colon transit, dyssynergic patterns, anorectal sensation, psychological distress, and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population, providing valuable insights into the pathophysiological underpinnings of these disorders.

Exercise is inversely associated with functional dyspepsia among a sample of Chinese male armed police recruits.

BACKGROUND: There is no study evaluating the association between exercise and functional dyspepsia (FD) based on the Rome IV criteria. We aimed to investigate the prevalence of FD and evaluate the association between exercise and FD based on Rome IV criteria among a sample of Chinese armed police recruits. METHODS: An on-site questionnaire survey on FD among a sample of Chinese armed police recruits was conducted based on the Rome IV criteria in 2021. Potential confounders included age, body mass index (BMI), race, marriage, education, smoking, and drinking variables were adjusted. RESULTS: A total of 2594 recruits were enrolled, including 46 FD participants and 2548 non-FD participants. In the model adjusted for all demographic variables among participants excluding irritable bowel syndrome (IBS) and functional constipation (FC), compared with no exercise participants, 1 h < each exercise time ≤ 2 h (OR = 0.15, 95% CI: 0.03-0.77, P = 0.0230) was inversely associated with FD and compared with no exercise participants, mild exercise (OR = 0.09, 95% CI: 0.01-0.71, P = 0.0220) was significantly inversely associated with FD. CONCLUSIONS: The incidence rate of FD in this sample Chinese armed police recruits was 1.77%, and 1 h < each exercise time ≤ 2 h and mild intensity exercise were independently inversely associated with FD. However, the causal relationship needs to be verified by further randomized controlled trials.

[Chronic abdominal pain from digestive origin : summary 2023]. / Douleur abdominale chronique d'origine digestive : synthèse 2023.

Chronic abdominal pain is continuous or intermittent pain that has been present for at least three months. As its clinical presentation and etiologies are numerous, recommendations to facilitate its management are difficult to establish. Unlike acute abdominal pain, which accounts for 5 to 10 % of emergency consultations, the prevalence of its chronic form is unknown. Its differential diagnoses are therefore important to know in order to direct initial management before referring to a specialist. The updated red flags were inspired by two journal articles dated 2021. It should now be considered that digestive neoplasia can be suspected before the age of 50, and that the prevalence of irritable bowel syndrome has decreased following a change in diagnostic criteria.

La douleur abdominale chronique est une douleur continue ou intermittente évoluant depuis au moins trois mois. Sa présentation clinique et ses étiologies étant nombreuses, des recommandations pour faciliter sa prise en charge sont difficiles à établir. Contrairement à la douleur abdominale aiguë, qui représente 5 à 10 % des consultations urgentes, la prévalence de sa forme chronique est inconnue. Ses diagnostics différentiels sont par conséquent importants à connaître afin de diriger la prise en charge initiale avant de référer à un-e spécialiste. La mise à jour des drapeaux rouges a été inspirée par deux articles de revue datés de 2021. Il faut désormais considérer qu'une néoplasie digestive peut être suspectée avant 50 ans et que la prévalence du syndrome de l'intestin irritable a diminué suite au changement des critères diagnostiques.

Menstrual Status Is Associated with the Prevalence of Irritable Bowel Syndrome in a Japanese Young Population: A Cross-Sectional Study.

INTRODUCTION: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. METHODS: Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. RESULTS: The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27-2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. CONCLUSION: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.

IBS randomized study: FODMAPs alter bile acids, phenolic- and tryptophan metabolites, while gluten modifies lipids.

Diet is considered a culprit for symptoms in irritable bowel syndrome (IBS), although the mechanistic understanding of underlying causes is lacking. Metabolomics, i.e., the analysis of metabolites in biological samples may offer a diet-responsive fingerprint for IBS. Our aim was to explore alterations in the plasma metabolome after interventions with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) or gluten versus control in IBS, and to relate such alterations to symptoms. People with IBS (n = 110) were included in a double-blind, randomized, crossover study with 1-wk provocations of FODMAPs, gluten, or placebo. Symptoms were evaluated with the IBS severity scoring system (IBS-SSS). Untargeted metabolomics was performed on plasma samples using LC-qTOF-MS. Discovery of metabolite alterations by treatment was performed using random forest followed by linear mixed modeling. Associations were studied using Spearman correlation. The metabolome was affected by FODMAP [classification rate (CR) 0.88, P < 0.0001], but less by gluten intake CR 0.72, P = 0.01). FODMAP lowered bile acids, whereas phenolic-derived metabolites and 3-indolepropionic acid (IPA) were higher compared with placebo. IPA and some unidentified metabolites correlated weakly to abdominal pain and quality of life. Gluten affected lipid metabolism weakly, but with no interpretable relationship to IBS. FODMAP affected gut microbial-derived metabolites relating to positive health outcomes. IPA and unknown metabolites correlated weakly to IBS severity. Minor symptom worsening by FODMAP intake must be weighed against general positive health aspects of FODMAP. The gluten intervention affected lipid metabolism weakly with no interpretable association to IBS severity. Registration: www.clinicaltrials.gov as NCT03653689.NEW & NOTEWORTHY In irritable bowel syndrome (IBS), fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) affected microbial-derived metabolites relating to positive health outcomes such as reduced risk of colon cancer, inflammation, and type 2 diabetes, as shown in previous studies. The minor IBS symptom induction by FODMAP intake must be weighed against the positive health aspects of FODMAP consumption. Gluten affected lipids weakly with no association to IBS severity.

Evaluation of the Impact of Some Single-Nucleotide Gene Polymorphisms on the Development of Adenomatous Polyps of the Colon in Patients with Irritable Bowel Syndrome.

BACKGROUND: The number of cases of irritable bowel syndrome is growing worldwide, in which adenomatous polyps can develop as a result of microinflammation of the colonic epithelium. Our study was aimed at the identification of the possible effect of single-nucleotide polymorphisms on the risk of the development of irritable bowel syndrome-related colonic adenomatous polyps. MATERIALS AND METHODS: The study involved 187 irritable bowel syndrome patients. The single-nucleotide polymorphisms were investigated by the polymerase chain reaction method and DNA was extracted with the phenol-chloroform: interleukin-1ß gene-31C/T (rs1143627), -511C/T (rs16944); interleukin-6 gene-174G/C (rs1800795); interleukin-10 gene-592C/A (rs1800872), -819T/C (rs1800871), -1082A/G (rs1800896); Toll-like receptor-2 gene Arg753Gln (rs5743708); Toll-like receptor-4 gene Thr399ile (rs4986791), Asp299Gly (rs4986790); and metalloproteinase-9 gene-8202A/G (rs11697325). The study of polymorphic loci was checked for compliance with the Hardy- Weinberg equilibrium using Fisher's exact test along with the analyses of the frequency of alleles and the genotypes. RESULTS: The association of diseases with G allele Toll-like receptor-2 gene Arg753Gln (rs5743708) was revealed in irritable bowel syndrome patients with adenomatous polyps of the colon (P < .0006) and AG single-nucleotide polymorphisms s of Toll-like receptor-2 gene (χ2 = 12.78, P < .002); A allele had a protective effect. The AG genotype metalloproteinase-9 gene-8202A/G (rs11697325) polymorphism in irritable bowel syndrome patients with adenomatous polyps of the colon had a protective effect (P < .05). AA genotype interleukin-10 gene-1082A/G (rs1800896) polymorphism in the irritable bowel syndrome patient (χ2 = 33.97, 4.0E-8) can be considered as the risk for adenomatous polyps of the colon in irritable bowel syndrome. CONCLUSION: G allele Toll-like receptor-2 gene Arg753Gln (rs5743708) and AA genotype interleukin-10 gene-1082A/G (rs1800896) polymorphisms can be the marker of the emergence of adenomatous polyps of the colon concomitant with irritable bowel syndrome.

Associations and gastrointestinal symptoms in women with endometriosis in comparison to women with irritable bowel syndrome: a study based on a population cohort.

BACKGROUND: Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. METHOD: The study cohort included women from the Malmö Offspring Study with information about endometriosis and IBS diagnoses from the National Board of Health and Welfare. The participants answered a questionnaire about lifestyle habits, medical and drug history, and self-reported IBS. The visual analog scale for IBS was used to estimate gastrointestinal symptoms the past 2 weeks. Endometriosis diagnosis and self-reported IBS were used as dependent variables to study associations with age, body mass index (BMI), education, occupation, marital status, smoking, alcohol habits, and physical activity using logistic regression. Mann-Whitney U Test or Kruskal-Wallis tests were used to calculate the differences in symptoms between groups. RESULTS: Of the 2,200 women with information from medical records, 72 participants had endometriosis; 21 (29.2%) of these had self-reported IBS. Of the 1,915 participants who had answered the questionnaire, 436 (22.8%) had self-reported IBS. Endometriosis was associated with IBS (OR:1.86; 95%CI:1.06-3.26; p = 0.029), as well as with age 50-59 years (OR:6.92; 95%CI:1.97-24.32; p = 0.003), age ≥ 60 years (OR:6.27; 95%CI:1.56-25.17; p = 0.010), sick leave (OR:2.43; 95%CI:1.08-5.48; p = 0.033), and former smoking (OR:3.02; 95%CI:1.19-7.68; p = 0.020). There was an inverse association with BMI (OR:0.36; 95%CI:0.14-4.91; p = 0.031). IBS was associated with endometriosis (OR:1.77; 95%CI:1.02-3.07; p = 0.041) and sick leave (OR:1.77; 95%CI:1.14-2.73; p = 0.010), with a tendency to association with smoking (OR:1.30; 95%CI:0.98-1.72; p = 0.071). When excluding participants using drugs associated with IBS, the condition was associated with current smoking (OR:1.39; 95%CI:1.03-1.89; p = 0.033) and inversely with age 50-59 years (OR:0.58; 95%CI:0.38-0.90; p = 0.015). There were differences in the gastrointestinal symptoms between IBS and healthy participants, but not between endometriosis and IBS or healthy participants. CONCLUSION: There were associations between endometriosis and IBS, without differences in gastrointestinal symptoms. Both IBS and endometriosis were associated with smoking and sick leave. Whether the associations reflect causality or depend on common risk factors and pathogenesis remains to be determined.

Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.

BACKGROUND: Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. METHODS: Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). KEY RESULTS: Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). CONCLUSIONS AND INFERENCES: Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.

Comorbidities, biomarkers and cause specific mortality in patients with irritable bowel syndrome: A phenome-wide association study.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete. OBJECTIVE: To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality. METHODS: We analyzed data from the population-based cohort of the UK Biobank (UKB) with 493,974 participants, including self-reported physician-diagnosed (n = 20,603) and ICD-10 diagnosed (n = 7656) IBS patients, with a mean follow-up of 11 years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients. RESULTS: In PheWAS analyses, 260 PheCodes were significantly overrepresented in self-reported physician-diagnosed IBS patients, 633 in patients with ICD-10 diagnosed IBS (ICD-10-IBS), with 221 (40%) overlapping. In addition to gastrointestinal diseases, psychiatric, musculoskeletal, and endocrine/metabolic disorders represented the most strongly associated PheCodes in IBS patients. Self-reported physician-diagnosed IBS was not associated with increased overall mortality and the risk of death from cancer was decreased (hazard ratio [HR] = 0.78 [95% CI = 0.7-0.9]). Lastly, we evaluated changes in serum metabolites in IBS patients and identified glycoprotein acetyls (GlycA) as a potential biomarker in IBS. One standard deviation increase in GlycA raised the risk of self-reported IBS/ICD-10 coded by 9%-20% (odds ratio [OR] = 1.09 [95% CI = 1.1-1.1]/OR = 1.20 [95% CI = 1.1-1.3]) and the risk of overall mortality in ICD-10-IBS patients by 28% (HR = 1.28 [95% CI = 1.1-1.5]). CONCLUSION: Our large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients.