Irritable Bowel Syndrome Cohort Research Articles

Bidirectional association between type 2 diabetes and irritable bowel syndrome: A large-scale prospective cohort study.

To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort. Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs). In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings. T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases.

Co-Morbidities of Irritable Bowel Syndrome in a Racially and Ethnically Diverse Population.

Introduction: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI), and associated co-morbidities worsen quality of life. Research concerning IBS co-morbidities in different racial/ethnic groups is very sparse. This study aimed to determine the prevalence rates of co-morbidities and possible differences in a multiracial/ethnic IBS cohort. Methods: Based on ICD-9-coded IBS diagnosis, 740 outpatients (≥18 years) were included in this retrospective study at Boston Medical Center. Demographics and ICD-9-coded co-morbidities were extracted from electronic records. Descriptive statistics and multiple logistic regression were used for data analyses. Results: The most prevalent co-morbidities in this IBS cohort included gastroesophageal reflux disorder (GERD) (30%), depression (27%), anxiety (23%), (chronic obstructive pulmonary disease) COPD/asthma (16%), and obesity (10%). GERD was more prevalent in Hispanics and Blacks (p = 0.0005), and non-ulcer dyspepsia (NUD) was more prevalent in Blacks and Asians (p = 0.003). Higher rates of diabetes mellitus type 2 (DMT2) (p = 0.0003) and depression (p = 0.03), but not anxiety (p = 0.9), were present in Blacks and Hispanics. GERD was significantly associated with Hispanics (p = 0.003), dependent on age, overweight, and obesity. NUD was significantly associated with Blacks (p = 0.01) and Asians (p = 0.006), independent of sex, age, and BMI. Cancer of the thyroid, ovaries, and testis occurred at a five-fold higher rate than expected. Conclusions: Significant racial/ethnic differences exist for IBS co-morbidities in this study cohort, including depression, DMT2, GERD, and NUD. Certain cancers were found to be more frequent in this IBS sample as compared with the general population.

Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital.

(1) Background: Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut-brain interaction (DGBI) that is known to reduce the quality of life and raise healthcare costs. The aim of this study was to describe the epidemiology of IBS in a large multiracial academic safety-net hospital. (2) Methods: An electronic query was performed using ICD-9 codes to identify 740 IBS outpatients seen at the Boston Medical Center (BMC) between 1 January 2005 and 30 September 2007. Demographic data were collected from electronic medical records. Bivariate analyses using chi-square tests and ANOVA were used to calculate the significance of categorical and continuous dependent variables, respectively. (3) Results: Compared with the general BMC outpatient population, the IBS cohort consisted of significantly higher proportions of White and Asian patients and lower proportions of Black and Hispanic patients (p < 0.0001). White and Asian patients predominantly had private insurance, while Black and Hispanic patients mostly had government/state-funded or no insurance (p < 0.0001). The IBS subgroup frequencies were similar across racial groups; however, Hispanic patients had IBS with constipation (32%, p < 0.02) more often compared to non-Hispanic patients. (4) Conclusions: Significant differences were found across the racial groups studied in this large outpatient IBS cohort. These findings are likely attributed to racial and socioeconomic disparities in healthcare access and utilization.

The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.

P103 Natural compounds in Ulcerative Colitis and Irritable Bowel Syndrome: Insights from immune-metabolic profiles

Abstract Background Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) represent chronic and occasionally disabling conditions, necessitating innovative treatment strategies. Covering 14% of Ireland's landscape, bogland ecosystems house unique plant biodiversity, yielding biologically active secondary metabolites. Informed by traditional medicinal knowledge and in vitro screening for immunomodulatory potential, three plant extracts (NTP0226A, NTP0127B, NTP0206EA) were selected for exploration of their potential to treat IBD and IBS within the "Unlocking Nature’s Pharmacy from Bogland Species" project. Methods Patients undergoing colonoscopy were prospectively recruited in three cohorts: healthy controls, IBS, and ulcerative colitis (UC). Recto-sigmoid biopsies were collected and cultured for 24 h with treatments (Infliximab, NTP0226A, NTP0127B, NTP0206EA). Colonic tissue explants underwent real-time energy metabolism profiling and quantification of 10 inflammatory mediators using Seahorse Xfe24 analyser and multiplex ELISA, respectively. P values &amp;lt;0.05 were considered significant in analyses. Results Twenty-seven patients were recruited (6 healthy controls, 6 IBS, and 15 UC). UC patient explants exhibited elevated glycolytic metabolism and increased IL-4, IL-6, and IL-12p70 secretion compared to non-UC patients. No differences were observed between healthy controls and IBS patients. Linear regression did not show correlation between age and mitochondrial bioenergetics. There was no change in metabolism profiles of any cohort following treatment with Infliximab or the 3 novel extracts. In the UC tissue, treatment with Infliximab reduced IL-12p70 secretion (p=0.0098), this reduction was not seen in the other 2 cohorts. NTP0206EA reduced IL-10 secretion in the UC cohort (p=0.0255). In the IBS cohort; NTP0127B reduced IL-10 secretion (p=0.0048) and NTP0226A reduced IL-4 (p=0.004) and IL-6 (p=0.0219) secretion. Principal component analysis demonstrated reduced separation between the immune-metabolic profiles of UC patients and healthy controls following treatment with NTP0226A (Figure 1). Conclusion Using an explant model, we have shown that UC patients have a distinct immune-metabolic profile modifiable by a standard IBD therapy and novel plant extracts. Blockade of IL-6 trans-signalling has recently shown promise as an effective treatment target in IBD. Our natural extract NTP0226A reduced IL-6 secretion in IBS patients and is a promising candidate for therapeutic exploration. These findings contribute to our understanding of the complex interplay in the colonic microenvironment and highlight potential avenues for novel therapeutic interventions.

Mucosa-Associated Microbiota Dysbiosis in the Terminal Ileum Correlates With Bowel Symptoms in Diarrhea-Predominant Irritable Bowel Syndrome.

The mucosa-associated microbiota (MAM) is not as frequently studied in diarrhea-predominant irritable bowel syndrome (IBS-D) compared with the fecal microbiota. In this study, we examined the MAM in the terminal ileum and its correlation with bowel symptoms in IBS-D. Mucosal biopsies of the terminal ileum from 25 patients with IBS-D and 25 healthy controls were collected for 16S ribosomal RNA gene sequencing. Correlation analysis was performed. Compared with healthy controls, the MAM in the terminal ileum showed a decreased alpha diversity in the IBS-D cohort (Chao1 and Shannon indexes, P < 0.05). And the overall MAM profile clustered separately into 2 groups (ADONIS [PERMANOVA, permutational multivariate analysis of variance], P < 0.05). At the phylum level, the relative abundance of Proteobacteria was significantly higher in the ileal MAM of patients with IBS-D while that of Firmicutes was significantly lower. At the genus level, the relative abundance of Pseudomonas was significantly higher in the IBS-D cohort, with lower Bacteroides and Ruminococcus . Moreover, 40.0% of patients with IBS-D had multiple small nodules (nodular lymphoid hyperplasia) on the mucosal surface of the terminal ileum, which indicated a low-grade inflammation. In patients with IBS-D with nodular lymphoid hyperplasia, the changes of Pseudomonas and Bacteroides were more overt. Correlation analysis revealed that the relative abundance of Pseudomonas positively correlated with abdominal pain and the severity of IBS. Patients with IBS-D showed a dysbiosis of MAM in the terminal ileum, which may be associated with bowel symptoms. Moreover, 40.0% of them displayed mucosal low-grade inflammation, with a more severe mucosal microbial disturbance.

Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau.

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

Age Differences in Core Symptoms and Symptom Relationships in Patients With Irritable Bowel Syndrome: A Network Analysis.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age. Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify the core symptoms driving the symptom structure between young (≤45 years) vs older (>45 years) adults with IBS. We evaluated 3 network properties between the 2 age groups: network structure, edge (connection) strength, and global strength. In both age groups, fatigue was the top core symptom. Anxiety was a second core symptom in the younger age group, but not the older age group. Intestinal gas and/or bloating symptoms also exerted considerable influences in both age groups. The overall symptom structure and connectivity were found to be similar regardless of age. Network analysis suggests fatigue is a critical target for symptom management in adults with IBS, regardless of age. Comorbid anxiety is likely an important treatment focus for young adults with IBS. Rome V criteria update could consider the importance of intestinal gas and bloating symptoms. Additional replication with larger diverse IBS cohorts is warranted to verify our results.

Comorbid extra-intestinal central sensitization conditions worsen irritable bowel syndrome in primary care patients.

Irritable bowel syndrome (IBS) is characterized as a central sensitization syndrome (CSS), a group of conditions including fibromyalgia, chronic fatigue, and restless leg syndrome (RLS) among others with frequent comorbidities of anxiety, depression, and chemical sensitivity. The prevalence of comorbid conditions and their impact on IBS symptom severity and quality of life in rural community populations has not been described. We administered a cross-sectional survey to patients with a documented CSS diagnosis in rural primary care practices to evaluate the relationship between CSS diagnoses, quality of life, symptom severity, and interactions with healthcare providers utilizing validated questionnaires. Subgroup analysis was performed on the IBS cohort. Mayo Clinic IRB approved the study. Seven hundred seventy-five individuals out of 5000 completed the survey (15.5% response rate) with 264 (34%) reporting IBS. Only 3% (n= 8) of IBS patients reported IBS alone without comorbid CSS condition. Most respondents reported overlapping migraine (196, 74%), depression (183, 69%), anxiety (171, 64%), and fibromyalgia (139, 52%). IBS patients with more than two comorbid CS condition showed significantly higher symptom severity with linear increase. Quality of life was lower in IBS with comorbid conditions, particularly in patients with IBS and RLS (mean EQ5-D 0.36 vs. 0.8 in IBS only, p< 0.01). Quality of life declined as number of comorbid conditions increased. Patients with IBS often have multiple CS disorders which increases symptom severity and lowers quality of life. Understanding the impact of multiple CSS diagnoses and treating these as a global condition may improve patient experience.

An Updated Comparative Study on the Impact of COVID-19 Infection and Vaccination in Patients with Inflammatory Bowel Disease and Irritable Bowel Syndrome

This study assessed the differences in swabbing rates, vaccine uptake, COVID-19 infection, hospitalization rates and outcomes in patients suffering from inflammatory bowel disease (IBD) on immunomodulation and patients diagnosed with irritable bowel syndrome (IBS). A population consisting of 250 IBD and 250 IBS patients was randomly selected from the local database. Apart from demographic data, the following data was collected: number of COVID-19 swabs taken, vaccination rates, type of vaccine administered, infection secondary to COVID-19, hospitalization and outcomes. IBD patients performed significantly more swabs tests for SARS-CoV-2 detection compared with IBS patients in both phases of the study. Whilst the IBS cohort recorded a larger number of COVID-19 infection and less hospitalisations whilst infected, IBD patients had a better outcome whilst infected since hospitalisation reason in the latter was not related to COVID-19 infection. IBD patients had a larger uptake of COVID-19 vaccines. This study was the first of its nature locally and internationally as it compared two unrelated cohorts of patients followed up in gastroenterology. Vaccination rates in both cohorts were higher than those reported internationally. In concordance with international studies, IBD patients are not at an increased risk of worse outcomes from COVID-19 infection compared to non-IBD cohorts.

S529 Do Social Determinants of Health Impact Which Patients Are Referred for the Low FODMAP Diet?

Introduction: The aim of this study was to explore if differences in social determinants of health in irritable bowel syndrome (IBS) patients impact access to the low FODMAP diet (LFD). Methods: A prospective cross-sectional survey of 486 adults was performed from May – June 2022. All respondents completed a 31-question survey via Survey Monkey. The survey link was distributed via social media platforms, low FODMAP dietician blog posts, and the IFFGD newsletter. Questions consisted of social determinants, such as the number of family members in their home, education attainment, employment status, healthcare insurance, access to healthcare, housing, utilities, transportation, childcare, and food access and insecurities. Statistical analyses included the Mann-Whitney U test and chi-square test. A p-value of ≤ 0.05 was considered statistically significant. Results: 462/486 (95.1%) respondents reported a diagnosis of IBS. Patients without a diagnosis of IBS were removed from the analysis. IBS cohort demographics consisted of 93% female, 92.5% Caucasian, and 92.7% residing in the United States. The primary IBS complaint was equally distributed: IBS-Diarrhea (35.1%), IBS-Constipation (29.1%), and IBS-Mixed (35.1%). 83.6% (n = 400) of IBS respondents were recommended the low FODMAP diet for treatment of their GI symptoms by a medical provider. IBS respondents were divided into two groups: IBS-LFD+ (n = 400, those referred for low FODMAP diet education) and IBS-LFD- (n = 62, those not referred for low FODMAP diet education). Compared with their IBS-LFD+, IBS-LFD- respondents had a lower education level (14.8% with high school diploma or less vs. 5.8%, p =0.01), lower household income (46.7% with income ≤ $74,999 vs. 30.7%, p =0.03), and decreased access food when needed (8.1 vs. 2.8 %, p = 0.03). IBS-LFD- respondents were also less likely start a low FODMAP diet on their own compared to IBS-LFD+ counterparts (12.4% vs. 87.6%, p < 0.001). Conclusion: IBS patients with a lower socioeconomic position were less likely to be recommended the low FODMAP diet as treatment compared to patients with higher socioeconomic positioning. This raises concern socioeconomic status negatively impacts referral for low FODMAP diet for IBS management and suggests implicit referral bias. Given the increasing evidence for dietary therapy for managing GI symptoms, further investigation is needed to identify how provider perceptions of patients influence dietary treatment recommendations. Table 1. - Comparison of social determinants between IBS patients recommended vs. NOT recommended the low FODMAP diet by their health provider Social Determinant Variable IBS patients recommended low FODMAP Diet [IBS-LFD+](n = 400) IBS patients NOT recommended low FODMAP Diet[IBS-LFD-](n = 62) P-Value Cramer V Coefficient Odds Ratio (OR) 95% Confidence Interval (CI) Highest Level of Education Attainment High school diploma/ GED or less 5.8% 14.8% 0.01 0.12 2.31 1.26, 4.25 ≥ High School Diploma/GED 94.2% 85.2% Household Income $0.00 - $74,999 30.7% 46.7% 0.03 0.11 1.81 1.05, 3.11 ≥ $75,000 69.3% 53.3% Access to Food When Needed Unable to access food when needed 2.8% 8.1% 0.03 0.10 2.45 1.14, 5.26 Likely to start low FODMAP diet on their own Yes 87.6% 12.4% < 0.001 0.19 0.28 0.16, 0.50 No 56.6% 44.4% Visit a registered dietitian about the low FODMAP diet Yes 88.2% 11.8% 0.06 0.09 0.64 0.40, 1.03 No 81.6% 18.4%

Discrete Choice Experiment Reveals Strong Preference for Dietary Treatment Among Patients With Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder of the gut-brain interaction that significantly affects quality of life. Several treatments, with comparable clinical efficacy, are available. Patient preferences can therefore be an important determinant of an effective management strategy. Treatment preferences of patients regarding decision making remain unclear. We aimed to examine these preferences and estimate trade-offs between different attributes. A total of 427 patients from the Maastricht IBS cohort were invited to participate. A labeled discrete choice experiment survey, containing 9 scenarios with each 3 alternatives (medication, diet, psychotherapy), was developed in order to estimate preferences. The treatment scenarios were based on 6 attributes: effectiveness, time to response, time until recurrence, side effects, time required, and frequency of appointments. The preference weights and relative importance were analyzed using a mixed logit model. A total of 185 (43.3%) of 427 potential respondents completed the questionnaire (mean age 49.51 years, 69.2% female). The most preferred treatment was dietary intervention (48.1%), followed by pharmacotherapy (29.2%) and psychotherapy (22.7%). IBS patients preferred a higher effectiveness, shorter time interval to response, longer time interval until recurrence, no severe side effects, and frequent appointments when attending psychotherapy. Younger patients (≤50 years of age) preferred dietary interventions and a long period until recurrence, whereas older patients (&gt;50 years of age) were more inclined to choose pharmacotherapy and the period until recurrence was not important. Dietary interventions were the most preferred IBS therapy. Identifying patients' treatment preferences during shared decision making will provide more optimal management strategies and could be the best approach to diminish disease burden.

P307 The effect of COVID-19 infection and vaccination in patients with Inflammatory Bowel Disease and Irritable Bowel Syndrome

BackgroundInflammatory Bowel Disease(IBD) and Irritable Bowel Syndrome(IBS) are gastrointestinal disorders which differ in pathophysiology and management. The use of immunomodulatory drugs brings concerns which increased during the pandemic. Similarly, patients with IBS may have concerns about the effect of infection and vaccine on their wellbeing. The aim of this study was to assess for any differences in swabbing, vaccine uptake, COVID-19 infection, hospitalisation rates and outcomes in patients with IBD on immunomodulatory treatment and patients with IBS.MethodsPatients were recruited through the local database (March, 2020 – August, 2021). All IBD patients had a histological diagnosis while IBS patients were diagnosed according to ROME IV criteria. All patients were offered vaccination. Apart from demographic data the following was collected: number of COVID-19 swabs taken, vaccination rates, type of vaccine administered, infection secondary to COVID-19, hospitalization and outcomes.ResultsOverall, 250 IBD patients (43.6% female) and, 250 patients with IBS (78.4% female) were recruited. The mean patient age in the IBS cohort was, 40.6 years (SD ±, 11.99) whilst the mean patient age in the IBD cohort was, 40.7 years (SD±15.7).Patients with IBD underwent significantly more COVID-19 swab tests (n=759) than patients with IBS (n=615) (p =0.02).Patients with IBD were having the following biological therapy:, 62.8% Infliximab, 24.8% Adalimumab, 10% Vedolizumab and, 2.4% Ustekinumab.There was no significant difference in COVID-19 infection rate between the IBS cohort (8.8%; n=22 patients;, 2 patients not vaccinated) and the IBD cohort (6.4%; n=16 patients;, 3 patients not vaccinated)(p=0.3). The vaccine uptake rate was similar (IBD:, 91.2%, IBS: 90%).Table, 1 demonstrates the type of vaccine administered to both cohorts.In the IBS cohort, 1 patient was admitted to hospital in view of symptomatic hypoxaemia. The patient was treated with oxygen and dexamethasone, but did not require ventilatory support. Within the IBD cohort, 3 patients requiring admission for IBD related treatment, tested positive asymptomatically on pre-admission COVID-19 screening. All had an uneventful outcome.Table 1CohortPfizerAstraZenecaJohnson&JohnsonModernaIBD43%54%1%2%IBS57%31%7%5%ConclusionThis study demonstrates that vaccine uptake, Covid-19 infection rates and outcomes were similar in patients with IBS and IBD patients on immunosuppressive therapy. However, IBD patients underwent significantly more swabbing than patients with IBS and this was generally due to patient concern of acquiring Covid-19 while being on immunosuppresive medications. This added psychological burden may further impact patients’ psychological state and thus their quality of life.

The role of the gut microbiome in paediatric irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common and disabling condition in children. The pathophysiology of IBS is thought to be multifactorial but remains incompletely understood. There is growing evidence implicating the gut microbiome in IBS. Intestinal dysbiosis has been demonstrated in paediatric IBS cohorts; however, no uniform or consistent pattern has been identified. The exact mechanisms by which this dysbiosis contributes to IBS symptoms remain unknown. Available evidence suggests the imbalance produces a functional dysbiosis, with altered production of gases and metabolites that interact with the intestinal wall to cause symptoms, and enrichment or depletion of certain metabolic pathways. Additional hypothesised mechanisms include increased intestinal permeability, visceral hypersensitivity and altered gastrointestinal motility; however, these remain speculative in paediatric patients, with studies limited to animal models and adult populations. Interaction between dietary components and intestinal microbiota, particularly with fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), has drawn increasing attention. FODMAPs have been found to trigger and worsen IBS symptoms. This is thought to be related to products of their fermentation by a dysbiotic microbial population, although this remains to be proven. A low-FODMAP diet has shown promising success in ameliorating symptoms in some but not all patients. There remains much to be discovered about the role of the dysbiotic microbiome in paediatric IBS.

Overlap between irritable bowel syndrome and hypermobile Ehlers-Danlos syndrome: An unexplored clinical phenotype?

Irritable bowel syndrome (IBS) is common, but its cause remains unknown. IBS patients present with gastrointestinal (GI) symptoms such as abdominal pain with altered bowel habits; however, some patients also have non-GI symptoms including muscle and joint pains. It is thus plausible that within large IBS cohorts, subgroups exist with distinct clinical phenotypes. Yet, these subgroups have not been clearly identified or characterized. Due to lack of segmentation, treatment-focused symptomatic management is similar for all with IBS and follows indiscriminate algorithms regardless of possible differing clinical phenotype. This universal approach to IBS management may account for the reported lack of efficacy of treatment. One emerging subgroup receiving increasing attention is that with overlap IBS and the underlying heritable connective tissue disorder, hypermobile Ehlers-Danlos syndrome (hEDS). Current evidence suggests that up to 62% of patients with hEDS suffer from IBS. However, despite recognition of the presence of IBS in hEDS, this overlap IBS/hEDS group has not been characterized and these patients are managed in a similar way to those with IBS alone. Future studies are required to characterize and deep phenotype in this overlap IBS/hEDS group.

Irritable bowel syndrome and subsequent risk of Parkinson's disease: a nationwide population-based matched-cohort study.

Gastrointestinal dysfunction (GI) is the most prevalent non-motor symptom of Parkinson's disease (PD), and its role in the risk of PD has been studied. In this study, we tried to evaluate whether irritable bowel syndrome (IBS) increased the risk of PD development stratified by sex, age, and IBS duration using a large nationwide cohort in Korea. Patients aged ≥ 20years with a primary diagnosis of IBS (ICD-10 codes: G56) more than three times were selected. A randomly matched cohort without IBS was enrolled by exact matching patients for sex, age, socioeconomic status, comorbidities, and year of enrollment to the IBS group with a ratio of 1:3. Cause-specific Cox regression models were used to identify hazards associated with PD development depending on the presence of IBS during the 11-year follow-up period. In total, 285,064 patients were enrolled in the study: 71,806 in the IBS cohort and 213,258 in the comparison cohort. Cause-specific Cox regression model showed a hazard ratio of 1.436 (95% CI, 1.226-1.682) for PD development in the IBS cohort, which is consistent in both male and female sexes. Subgroup analyses according to age groups showed that IBS increased PD risk only in individuals ≥ 65years (HR = 1.449, 95% CI, 1.207-1.741). We found temporal relationship between IBS and PD at aged ≥ 65years. There might be a possibility that IBS was an early manifestation of PD, and future studies for causal link between the two diseases to elucidate biomechanism are warranted.

Frequency of Irritable Bowel Syndrome in Patients with Brugada Syndrome and Drug-Induced Type 1 Brugada Pattern

Irritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Prevalence of FBDs over a 12 months period were compared between probands with BrS/drug-induced type 1 Brugada pattern (DI-Type 1 BrP) (n = 148) and a control group (n = 124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type 1 BrP and 8.1% in the control group (p = 2.34 × 10-4). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p = 0.033) was a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/DI-Type 1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. In conclusion, IBS is a common co-morbidity in patients with BrS/DI-Type 1 BrP. Presence of current and/or history of migraine are a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type 1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype.

Healthcare spending and utilization for pediatric Irritable Bowel Syndrome in a commercially insured population.

Pediatric Irritable Bowel Syndrome (IBS) is common and can be associated with disabling gastrointestinal symptoms. Comprehensive data regarding utilization and cost of pediatric IBS are lacking. Our aim was to determine the annual all-cause spending and healthcare utilization in pediatric IBS. Cross-sectional cohort study using a national claims database of commercially insured individuals. 932,592 members, age 8-18years, were included. Members were selected based on PheWas codes and continuous enrollment in 2014. Linear and binomial regression models were used to calculate healthcare spending and compare comorbidities between IBS subjects and controls. 1215 members with claims for IBS (68.4% female) and 931,377 controls (55.7% female) were included. Mean age was 15.03±2.83 (median 16) years in the IBS group and 13.14±3.12 (median 13) years in controls. Mental health and chronic pain comorbidities were more prevalent in the IBS cohort. Healthcare spending: The mean annual all-cause incremental spending of members with IBS was $6,364.60 compared to controls when adjusting for age and gender. Healthcare utilization: Members with IBS had increased healthcare utilization including higher rates of inpatient, outpatient, and emergency room visits, and higher rates of health service utilization including medical care, radiology/laboratory services, surgery, anesthesia, mental health, and physical therapy. General pediatrics was more frequently consulted by controls. All subspecialty consultations, with the exception of dental medicine and endocrinology, were sought more frequently by IBS patients. Patients with IBS incur significant annual spending through increased healthcare utilization.

Does irritable bowel syndrome increase the risk of interstitial cystitis/bladder pain syndrome? A cohort study of long term follow-up.

Interstitial cystitis/bladder pain syndrome (IC/BPS) and irritable bowel syndrome (IBS) often occur concomitantly without an obvious reason. It is important to determine the relationship between these related diseases. We aimed to determine whether IBS increase the risk of IC/BPS. We identified newly diagnosed IBS patients between 2002 and 2013 from a nationwide database as the IBS cohort. Subjects diagnosed with IC/BPS before IBS were excluded. Cox's regression analysis with a hazard ratio (HR) of IC/BPS between IBS and the non-IBS cohort was applied to unmatched and matched (16 confounders of propensity scores) models. The time from diagnosis of IBS to IC/BPS was also calculated. In the unmatched group, which included 100,124 IBS (55% female) and 874,048 non-IBS patients, the IC/BPS adjusted HR was 1.292 (95% confidence interval [CI], 1.131-1.476;p < 0.0001) in the IBS cohort compared with the non-IBS cohort. In the matched group, there were 85,359 patients in each cohort, and the IC/BPS HR was 1.599 (95% CI, 1.344-1.903; p < 0.0001). The average numbers of years until the development of IC/BPS in the IBS cohort and non-IBS cohort were 4.60 ± 2.58 (n = 253) and 5.99 ± 3.49 (n = 295) years, respectively. IBS was shown to increase the risk of IC/BPS in this 12-year cohort study. The time from the diagnosis of IBS to IC/BPS was 5.35 ± 3.18 years. A common pathophysiology of IBS and IC/BPS is possible. Clinicians should be mindful of the association and promote collaborative care of these two elusive diseases.

Identifying a biological signature of prenatal maternal stress.

Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation, which can negatively affect fetal development. We investigated a panel of circulating markers as a biological signature of this stress exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers of GI permeability and inflammation were measured in plasma from healthy and IBS cohorts of women at 15 and 20 weeks’ gestation. Biomarkers were evaluated with respect to their degree of association to levels of stress, anxiety, and depression as indicated by responses from the Perceived Stress Scale, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. High levels of stress were associated with elevations of soluble CD14, lipopolysaccharide binding protein (LBP), and tumor necrosis factor–α, while anxiety was associated with elevated concentrations of C-reactive protein (CRP) in otherwise healthy pregnancies. Prenatal depression was associated with higher levels of soluble CD14, LBP, and CRP in the healthy cohort. High levels of prenatal anxiety and depression were also associated with lower concentrations of tryptophan and kynurenine, respectively, in the IBS cohort. These markers may represent a core maternal biological signature of active prenatal stress, which can be used to inform intervention strategies via stress reduction techniques or other lifestyle approaches. Such interventions may need to be tailored to reflect underlying GI conditions, such as IBS.