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Background: Disorders of gut-brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world., Methods: We performed an ecological study utilizing peer-reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI)., Key Results: The regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = -0.57, 95% CI: -0.92, -0.22, p = 0.002) and happiness scores (β = -0.433 95% CI: 0.821, -0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = -0.50, 95% CI: -0.86, -0.13, p = 0.01) and happiness scores (β = -0.497, 95% CI: -0.863, -0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = -0.43, 95% CI: -0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = -0.40, 95% CI: -0.79, -0.014, p = 0.043) and happiness scores (β = -0.390, 95% CI: -0.778, -0.003, p = 0.049)., Conclusions & Inferences: Utilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio-cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: This SRMA reviewed and assessed the changes in the severity of disorders of gut-brain interaction (DGBI) symptoms during the COVID-19 pandemic, and evaluated factors associated with symptom severity changes., Methods: Electronic databases were searched until February 2024, for articles reporting on changes in symptom severity in DGBI patients during the COVID-19 pandemic. The proportion of DGBI patients who reported a change in their symptom severity were pooled using a random-effects model, and subgroup analyses were conducted to assess the effect of socio-cultural modifiers on symptom severity in DGBI., Key Results: Twelve studies including 3610 DGBI patients found that 31.4% (95% CI, 15.9-52.5) of DGBI patients experienced symptom deterioration, while 24.3% (95% CI, 10.2-47.5) experienced improvement. Countries with high gross domestic product (GDP) had a 43.5% (95% CI, 16.3-75.2) likelihood of symptom deterioration, compared to 9.2% (95% CI, 1.4-42.2) in lower GDP countries. Similarly, countries with low COVID fatality rates had a 60.1% (95% CI, 19.7-90.3) likelihood of symptom deterioration, compared to 18.3% (95% CI, 7.8-36.9) in higher fatality rate countries. Countries with lenient COVID policies had a 58.4% (95% CI, 14.1-92.3) likelihood of symptom deterioration, compared to 19% (95% CI, 8.2-38.1) in countries with stricter policies. Patients in high vaccine hesitancy countries had a 51.4% (95% CI, 19.5-82.2) likelihood of symptom deterioration, compared to 10.6% (95% CI, 2.7-33.4) in low vaccine hesitancy countries., Conclusions & Inferences: This meta-analysis reveals that a significantly higher proportion of DGBI patients experienced deterioration of symptoms during the COVID-19 pandemic. Various sociocultural, economic and environmental factors potentially modify the effects of the COVID-19 pandemic on DGBI., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background and Aim: Patients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta-analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO., Methods: MEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model., Results: Final dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6-69.4), with substantial heterogeneity in this analysis (I 2  = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0-11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid-suppressing agents (72.0%, 95% CI 57.5-83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7-70.2)., Conclusions: This systematic review and meta-analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid-suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case-control studies and clinical heterogeneity seen in the studies., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Limited information is available about patterns of healthcare utilization for prevalent gastrointestinal conditions and their link to symptom burden., Aim: To identify patterns of healthcare utilization among outpatients with highly prevalent gastrointestinal conditions and define the link between healthcare utilization, symptom burden, and disease group., Methods: We randomly selected patients from the gastroenterology outpatient clinic at Princess Alexandra Hospital who had chronic gastrointestinal conditions such as constipation-predominant irritable bowel syndrome (IBS-C, n = 101), diarrhea-predominant IBS (IBS-D, n = 101), mixed IBS (n = 103), inflammatory bowel disease with acute flare (n = 113), IBD in remission (n = 103), and gastroesophageal reflux disease (n = 102). All had presented at least 12 months before and had a 12-month follow-up after the index consultation. Healthcare utilization data were obtained from state-wide electronic medical records over a 24-month period. Intensity of gastrointestinal symptoms was measured using the validated Structured Assessment of Gastrointestinal Symptoms (SAGIS) Scale. Latent class analyses (LCA) based on healthcare utilization were used to identify distinct patterns of healthcare utilization among these patients., Results: LCA revealed four distinct healthcare utilization patterns across all diagnostic groups: Group A: Emergency department utilizers, Group B: Outpatient focused care utilizers, Group C: Inpatient care utilizers and Group D: Inpatient care and emergency department utilizers. LCA groups with high emergency utilization were characterized by high gastrointestinal symptom burden at index consultation regardless of condition (Mean (standard deviation)) SAGIS score Group A: 24.63 (± 14.11), Group B: 19.18 (± 15.77), Group C: 22.48 (± 17.42), and Group D: 17.59 (± 13.74, p < 0.05)., Conclusion: Distinct healthcare utilization patterns across highly prevalent gastrointestinal conditions exist. Symptom severity rather than diagnosis, likely reflecting unmet clinical need, defines healthcare utilization., (© 2024. The Author(s).)

Introduction: The need for public research funding to be more accountable and demonstrate impact beyond typical academic outputs is increasing. This is particularly challenging and the science behind this form of research is in its infancy when applied to collaborative research funding such as that provided by the Australian National Health and Medical Research Council to the Centre for Research Excellence in Digestive Health (CRE-DH)., Methods and Analysis: In this paper, we describe the protocol for applying the Framework to Assess the Impact from Translational health research to the CRE-DH. The study design involves a five-stage sequential mixed-method approach. In phase I, we developed an impact programme logic model to map the pathway to impact and establish key domains of benefit such as knowledge advancement, capacity building, clinical implementation, policy and legislation, community and economic impacts. In phase 2, we have identified and selected appropriate, measurable and timely impact indicators for each of these domains and established a data plan to capture the necessary data. Phase 3 will develop a model for cost-consequence analysis and identification of relevant data for microcosting and valuation of consequences. In phase 4, we will determine selected case studies to include in the narrative whereas phase 5 involves collation, data analysis and completion of the reporting of impact.We expect this impact evaluation to comprehensively describe the contribution of the CRE-DH for intentional activity over the CRE-DH lifespan and beyond to improve outcomes for people suffering with chronic and debilitating digestive disorders., Ethics and Dissemination: This impact evaluation study has been registered with the Hunter New England Human Research Ethics Committee as project 2024/PID00336 and ethics application 2024/ETH00290. Results of this study will be disseminated via medical conferences, peer-reviewed publications, policy submissions, direct communication with relevant stakeholders, media and social media channels such as X (formely Twitter)., Competing Interests: Competing interests: NK, KD, SAR and MR disclose no conflicts. NT is Emeritus Editor-in-Chief of Medical Journal of Australia, Section Editor of Up to Date and has research collaborations with Intrinsic Medicine (human milk oligosaccharide), Alimentry (gastric mapping) and is a consultant for Agency for Health Care Research and Quality (fiber and laxation), outside the submitted work. In addition, he has licenced Nepean Dyspepsia Index (NDI) to MAPI, and Talley Bowel Disease Questionnaire licensed to Mayo/Talley, 'Diagnostic marker for functional gastrointestinal disorders' Australian Provisional Patent Application 2021901692, 'Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis' US Patent Application No. 63/537,725. GH received unrestricted educational support from the Falk Foundation. Research support was provided via the Princess Alexandra Hospital, Brisbane by GI Therapies, Takeda Development Center Asia, Eli Lilly Australia, F. Hoffmann-La Roche, MedImmune, Celgene, Celgene International II Sarl, Gilead Sciences, Quintiles, Vital Food Processors, Datapharm Australia Commonwealth Laboratories, Prometheus Laboratories, FALK GmbH & Co KG, Nestle, Mylan and Allergan (prior to acquisition by AbbVie). GH is also a patent holder for a biopsy device to take aseptic biopsies (US 20150320407 A1)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Issue Addressed: Colorectal cancer (CRC) screening through fecal occult blood testing (FOBT) has saved thousands of lives globally with multiple countries adopting comprehensive population wide screening programs. Participation rates in FOBT based CRC screening for the socially and economically disadvantaged remains low. The aim of this systematic review is to explore empirical evidence that will guide targeted interventions to improve participation rates within priority populations., Methods: PubMed, Embase, Scopus, Cinahl and PsycInfo were systematically searched from inception to 22 June 2022. Eligible studies contained qualitative evidence identifying barriers to FOBT based CRC screening for populations impacted by the social determinants of health. An inductive thematic synthesis approach was applied using grounded theory methodology, to explore descriptive themes and interpret these into higher order analytical constructs and theories., Results: A total of 8,501 publications were identified and screened. A total of 48 studies from 10 countries were eligible for inclusion, representing 2,232 subjects. Coding within included studies resulted in 30 key descriptive themes with a thematic frequency greater than 10%. Coded themes applied to four overarching, interconnected barriers driving inequality for priority populations: social, behavioural, economic and technical/interfaces. SO WHAT?: This study has highlighted the need for stronger patient/provider relationships to mitigate barriers to FOBT screening participation for diverse groups. Findings can assist health professionals and policy makers address the systemic exclusion of priority populations in cancer screening by moving beyond the responsibility of the individual to a focus on addressing the information asymmetry driving low value perceptions., (© 2023 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Introduction: An association between functional dyspepsia (FD) and wheat-containing foods has been reported in observational studies; however, an adaptive response has not been demonstrated. We examined whether antigens present in wheat could provoke a response from FD duodenal lymphocytes., Methods: Lamina propria mononuclear cells (LPMCs) were isolated from duodenal biopsies from 50 patients with FD and 23 controls. LPMCs were exposed to gluten (0.2 mg/mL) or gliadin (0.2 mg/mL) for 24 hours. Flow cytometry was performed to phenotype lymphocytes. Quantitative PCR was used to measure the expression of gliadin-associated T-cell receptor alpha variant ( TRAV ) 26-2., Results: In response to gliadin (but not gluten) stimulation, the effector Th2-like population was increased in FD LPMCs compared with that in controls and unstimulated FD LPMCs. Duodenal gene expression of TRAV26- 2 was decreased in patients with FD compared with that in controls. We identified a positive association between gene expression of this T-cell receptor variant and LPMC effector Th17-like cell populations in patients with FD, but not controls after exposure to gluten, but not gliadin., Discussion: Our findings suggest that gliadin exposure provokes a duodenal effector Th2-like response in patients with FD, supporting the notion that food antigens drive responses in some patients. Furthermore, these findings suggest that altered lymphocyte responses to wheat proteins play a role in FD pathogenesis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Rome criteria differentiate distinct types of disorders of gut-brain interaction (DGBI); also known as functional gastrointestinal disorders. Overlap of symptom categories frequently occurs. This systematic review and meta-analysis aimed to define the prevalence of DGBI overlap and compare overlap in population-based, primary care or tertiary care health settings. Furthermore, we aimed to compare symptom severity of psychological comorbidities in DGBI with and without overlap., Methods: For this systematic review and meta-analysis we searched MEDLINE (PubMed) and Embase electronic databases from inception until March 1, 2022, for original articles and conference abstracts of observational cross-sectional, case-controlled, or cohort design studies that reported the prevalence of DGBI overlap in adult participants (aged ≥18 years). We included only those studies where the diagnosis of DGBI was based on clinical assessment, questionnaire data, or specific symptom-based criteria. Studies were excluded if reporting on mixed populations of DGBI and organic diseases. Aggregate patient data were extracted from eligible published studies. The prevalence of DGBI overlap in all studies was pooled using the DerSimonian and Laird random effects model, and further analysis stratified by subgroups (care setting, diagnostic criteria, geographic region, and gross domestic product per capita). We also assessed the relationship between DGBI overlap with anxiety, depression, and quality of life symptom scores. This study was registered with PROSPERO (CRD42022311101)., Findings: 46 of 1268 screened studies, reporting on 75 682 adult DGBI participants, were eligible for inclusion in this systematic review and meta-analysis. Overall, 24 424 (pooled prevalence 36·5% [95% CI 30·7 to 42·6]) participants had a DGBI overlap, with considerable between-study heterogeneity (I 2 =99·51, p=0·0001). In the tertiary health-care setting, overlap among participants with DGBI was more prevalent (8373 of 22 617, pooled prevalence 47·3% [95% CI 33·2 to 61·7]) compared with population-based cohorts (11 332 of 39 749, pooled prevalence 26·5% [95% CI 20·5 to 33·4]; odds ratio 2·50 [95% CI 1·28 to 4·87]; p=0·0084). Quality of life physical component scores were significantly lower in participants with DGBI overlap compared with participants without overlap (standardised mean difference -0·47 [95% CI -0·80 to -0·14]; p=0·025). Participants with DGBI overlap had both increased symptom scores for anxiety (0·39 [95% CI 0·24 to 0·54]; p=0·0001) and depression (0·41 [0·30 to 0·51]; p=0·0001)., Interpretation: Overlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution., Funding: National Health and Medical Research Council and Centre for Research Excellence., Competing Interests: Declaration of interests GH has received payments or honoraria for lectures, presentations, or speakers bureaus from Bayer, and has also received travel/support for attending meetings from Bayer. He has participated on data safety monitoring boards or advisory boards from Australian Biotherapeutics, Glutagen, and Bayer. GH holds stock or stock options in Bayer. He serves on the boards of the West Moreton Hospital and Health Service (WMHHS), Queensland, UQ Healthcare, Brisbane, and is vice president of Gastro-Liga, Germany, and Chair of the WMHHS Board Quality and Safety Committee. He is on the Research Committee of the Royal Australasian College of Physicians. GH acknowledges funding from the National Health and Medical Research Council (NHMRC) for the Centre for Research Excellence in Digestive Health. GH holds a Medical Research Future Fund grant and an NHMRC ideas grant. NJT reports grants from NHMRC (Centre for Research Excellence in Digestive Health; investigator grant), HMRI, Defence department of the Australian government (Cognobiome grant), AusEE, Astra Zeneca, Allakos, and Intrinsic Medicine. He reports personal fees from Adelphi values, Allakos, Astra Zeneca, Bayer AG, Comvita Mānuka Honey, BluMaiden, twoXAR, Dr Falk Pharma/Jorveza, Glutagen, IsoThrive, Intrinsic Medicine, and Rose Pharma, and has acted as an educational speaker for GlaxoSmithKline Australia. He has non-financial support from Norgine for an IBS interest group. NJT has a patent for biomarkers of IBS licensed (#12735358·9 -1405/2710383 and #12735358·9 -1405/2710384), has licensed questionnaires (Talley Bowel Disease Questionnaire) to the Mayo Clinic, has a Nestec European Patent Application (No. 12735358·9), has a provision Australian patent application for a diagnostic marker for functional gastrointestinal disorders (2021901692), a Singapore provisional patent (NTU Ref: TD/129/17 “Microbiota Modulation Of BDNF Tissue Repair Pathway”), and copyright Nepean Dyspepsia Index (NDI) 1998. He has acted on an advisory board for Bristol Myers Squibb. NJT declares the following other financial or non-financial interests: Medical Journal of Australia (Editor in Chief), Up to Date (Section Editor), Precision and Future Medicine, Sungkyunkwan University School of Medicine, South Korea (Editorial Board Member), Med (Journal of Cell Press; Editorial Board Member), eGastroenterology (Editorial Board Member), and has received personal fees for a textbook from Elsevier. NJT has leadership or fiduciary roles (all unpaid) in the International Foundation for Functional Gastrointestinal Disorders (IFFGD; advisory board), AusEE (advisory board), OzSage, NHMRC Principal Committee (Research Committee), Asia Pacific Association of Medical Journal Editors (APAME), AAHMS, Rome V working team member (gastroduodenal committee), International Plausibility Project Co-Chair (Rome Foundation funded), COVID-19 vaccine forum member. WDC reports grants from Biomerica, Commonwealth Diagnostics International, QOL Medical, and Salix/Valeant, has received consulting fees from AbbVie, Alnylam, Biomerica, Gemelli, Ironwood, Isothrive, QOL Medical, Nestle, Redhill, Salix/Valenat, Urovant, Takeda, and Vibrant. He is on the board of trustees and an officer of the American College of Gastroenterology, board of directors of the Rome Foundation, and board of directors and is vice president of the IFFGD. TF, AS, NK, YYL, KAG, and MPG declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: The role of gastroscopy to investigate the upper GI (UGI) tract in subjects with a positive fecal occult blood test (FOBT+) result is controversial. We conducted a systematic review and meta-analysis, which aimed to determine the prevalence of UGI lesions in FOBT+ subjects., Methods: Databases were searched until March 31, 2022 for studies reporting UGI lesions in FOBT+ subjects undergoing colonoscopy and gastroscopy. Pooled prevalence rates of UGI cancers and clinically significant lesions (CSLs; lesions potentially explaining occult blood loss), odds ratio (OR), and 95% confidence intervals (CIs) were calculated., Results: We included 21 studies with 6993 FOBT+ subjects. Pooled prevalence of UGI cancers was .8% (95% CI, .4-1.6) and UGI CSLs was 30.4% (95% CI, 20.7-42.2), and that of colonic cancers and CSLs was 3.3% (95% CI, 1.8-6.0) and 31.9% (95% CI, 23.9-41.1), respectively. There was no significant difference in the prevalence of UGI CSL and UGI cancers in FOBT+ subjects with/without colonic pathology (ORs of 1.2 [95% CI, .9-1.6; P = .137] and 1.6 [95% CI, .5-5.5; P = .460]). Anemia in FOBT+ subjects was associated with UGI cancers (OR, 6.3; 95% CI, 1.3-31.5; P = .025) and UGI CSLs (OR, 4.3; 95% CI, 2.2-8.4; P = .0001). GI symptoms were not associated with UGI CSLs (OR, 1.3; 95% CI, .6-2.8; P = .511)., Conclusions: There is an appreciable prevalence of UGI cancers and other CSLs in FOBT+ subjects. Anemia but not symptoms or colonic pathology are linked to UGI lesions. Although the data suggest that same-day gastroscopy in FOBT+ subjects undergoing colonoscopy yields approximately 25% more malignancies as colonoscopy alone, prospective data are required to determine the cost-efficacy of dual endoscopy as a standard of care for all FOBT+ subjects., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Goals: We aimed to develop and validate a patient-reported experience measure for gastrointestinal (GI) endoscopy, the Comprehensive Endoscopy Satisfaction Tool that captures relevant domains that influence the patient's experience and identify factors that shape satisfaction., Background: Patient-reported experience measures are used to capture specific quality aspects of health care services. GI endoscopic services are high-volume services, and there is a lack of specific, validated instruments to capture various domains that shape the patients' experience with routine clinical endoscopic services., Study: After an environmental scan and structured literature review, focus groups with patients were conducted to identify relevant factors influencing the patient experience with GI endoscopic services. After an initial validation in 101 patients undergoing routine GI endoscopies, the instrument was tested in 7800 patients. In addition, the influence of sociodemographic factors on global satisfaction was explored., Results: The final version included 26 specific items plus 4 global ratings for preprocedure, experience on day of procedure, postprocedure care, and infrastructure. In addition, a global rating of the overall experience was included. Patient satisfaction was significantly higher in older patients (P<0.001) but not influenced by gender, nationality, marital status, education, or employment status. Interestingly, during periods of coronavirus disease-19-related service interruptions, the Net Promoter Score was significantly reduced (P<0.0001) providing evidence for the responsiveness of the instrument., Conclusions: The Comprehensive Endoscopy Satisfaction Tool is a valid measure for the patient experience with the various components of endoscopic services, allows for the identification of domains that impact on the patient experience and is a practical tool to compare patient satisfaction over time and across facilities., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In patients with primary sclerosing cholangitis (PSC), antimicrobial therapy with oral vancomycin (OV) is increasingly used to prevent progression of the liver disease and control concomitant ulcerative colitis (UC); however, there are concerns regarding the risk of development of vancomycin-resistant enterococci (VRE). Thus, we aimed to determine the incidence of VRE in PSC-UC patients. We conducted a retrospective study of PSC-UC patients, treated with OV at the Department of Gastroenterology at the Princess Alexandra Hospital. VRE testing was performed utilizing rectal swabs. We included 7 PSC-UC patients (age 22-53 years, 2 females) treated with OV with daily dose ranging from 250 to 1500 mg. All patients were treated for at least 6 months with OV (range 9-31 months, mean 32.1 months). All patients achieved complete clinical remission of the UC, with mean reduction of fecal calprotectin by 634 μg/mg (87.3%), mean reduction in the C-reactive protein by 21.9 mg/L (74.2%), and mean reduction in the total Mayo score by 9.3 (93.3%). With regard to the liver parameters, mean improvement in alkaline phosphatase enzyme and total bilirubin was -48.7 U/L (-19.7%) and -2.7 mg/dL (-19.6%), respectively. No patient treated with OV developed VRE or reported any adverse events. This cohort study including PSC-UC patients did not provide evidence for development of VRE, while treatment with vancomycin was associated with clinical and endoscopic remission of the UC. Larger, prospective trials are required to define the efficacy and safety of antimicrobial therapy in PSC-UC, while the risk of VRE appears small., (© 2022. The Author(s).)

Background & Aims: This study explored the link between duodenal eosinophils and mast cells in patients with functional dyspepsia (FD)., Methods: MEDLINE (PubMed) and Embase electronic databases were searched until June 2021 for case-control studies reporting duodenal eosinophils and mast cells in FD. Pooled standardized mean difference (SMD), odds ratio, and 95% CIs of duodenal eosinophils and mast cells in FD patients and controls were calculated, using a random-effects model., Results: Twenty-two case-control studies with 1108 FD patients and 893 controls were identified. Duodenal eosinophils (SMD, 1.29; 95% CI, 0.85-1.73; P = .0001) and mast cells (SMD, 2.11; 95% CI, 1.14-3.07; P = .0001) were increased in FD patients compared with controls. Substantial heterogeneity was found (I 2  = 93.61, P = .0001; and I 2  = 96.69, P = .0001, respectively) and visual inspection of funnel plots confirmed publication bias. Degranulation of duodenal eosinophils was significantly higher in FD patients compared with controls (odds ratio, 3.78; 95% CI, 6.76-4.48; P = .0001), without statistically significant heterogeneity. We conducted a sensitivity analysis for duodenal eosinophils, by including only high-quality studies, and the results remained unchanged (SMD, 1.73; 95% CI, 1.06-2.40; P = .0001), with substantial heterogeneity. Postinfectious FD patients had increased duodenal eosinophils compared with controls (SMD, 3.91; 95% CI, 1.32-6.51; P = .001) and FD patients without any history of infection (SMD, 1.42; 95% CI, 0.88-1.96; P = .001). Helicobacter pylori-negative FD patients had significantly higher duodenal eosinophils compared with controls (SMD, 3.98; 95% CI, 2.13-5.84; P = .0001), with substantial heterogeneity. No significant difference in duodenal eosinophils was seen according to FD subtypes., Conclusions: This meta-analysis suggests a link between duodenal microinflammation and FD. However, the quality of evidence is very low, largely owing to the unexplained heterogeneity and serious risk of publication bias in all comparative analyses. Thus, causality remains uncertain and further studies are required., (Copyright © 2022. Published by Elsevier Inc.)

Functional gastrointestinal disorders (FGID) such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent and debilitating attributed to altered gut function and gut-brain interactions. FGID can be reliably diagnosed based upon the symptom pattern; but in the clinical setting FD or IBS a frequent diagnoses of exclusion after relevant structural causes of symptoms have been ruled out by appropriate testing. Thus far, there is no established biomarker for FGIDs. To address this limitation, we utilised multi-omics and chemometrics integration to characterise the blood plasma biochemistry in patients with IBS, FD, an overlap of FD/IBS, and controls using liquid chromatography-mass spectrometry (LC-MS) techniques.Cholesterol metabolism products Cholest-5,24-dien-3β-ol, 3-O-β-D-glucopyranoside, energy pathway metabolites, immunoglobulin-γ2 and immunoglobulin-κ, and carbonic anhydrase-1 proteins were particularly elevated in IBS. Furthermore, arginine and proline metabolisms, thyroid hormone synthesis, ferroptosis and, complementary and coagulation cascades were particularly upregulated in patients with IBS. Cer(d18:1/26:1(17Z)) and PI(14:0/22:1(11Z)) lipids were elevated in FD and FD-IBS but were depleted in IBS. Markers of central carbon metabolism and lipidome profiles allowed better discrimination and model predictability than metaproteome profile in healthy and FGID conditions.Overall, the multi-omics integration allowed the discrimination of healthy controls and FGID patients. It also effectively differentiated the biochemistry of FGID subtypes including FD, IBS and FD-IBS co-occurrence. This study points towards the possibility of multi-omics integration for rapid and high throughput analysis of plasma samples to support clinicians screen and diagnose patients with suspected FGIDs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Antimicrobial therapy improves symptoms in patients with irritable bowel syndrome (IBS), but the efficacy in functional dyspepsia (FD) is largely unknown. While FD and IBS frequently overlap, it is unknown if concomitant IBS in FD alters the response to antimicrobial therapy in FD. Thus, we aimed to assess and compare the effect of antimicrobial therapy on visceral sensory function and symptom improvement in FD patients with and without IBS., Methods: Adult patients with FD with or without IBS received rifaximin 550 mg BD for 10 days, followed by a 6-week follow-up period. The total gastrointestinal symptom score as measured by the SAGIS (Structured Assessment of Gastrointestinal Symptoms) questionnaire and subscores (dyspepsia, diarrhea, and constipation), symptom response to a standardized nutrient challenge and normalization of the glucose breath tests were measured., Results: Twenty-one consecutive adult patients with FD and 14/21 with concomitant IBS were recruited. Treatment with rifaximin resulted in a significant (p = 0.017) improvement in the total SAGIS score from 34.7 (± 15.4) at baseline to 26.0 (± 16.8) at 2 weeks and 25.6 (± 17.8) at 6 weeks post-treatment. Similarly, compared to baseline there was a statistically significant improvement in SAGIS subscores for dyspepsia and diarrhea (all p < 0.05) and effects persisted for 6 weeks post-treatment. Similarly, the symptom score (and subscores) following a standardized nutrient challenge improved significantly (p < 0.001) 2 weeks post-treatment. The presence of concomitant IBS did not significantly influence the improvement of symptoms after antibiotic therapy (all p > 0.5)., Conclusions: In FD patients, the response to antimicrobial therapy with rifaximin is not influenced by concomitant IBS symptoms., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic-pituitary-adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: This systematic review and meta-analysis aimed to determine the role of small intestinal bacterial overgrowth (SIBO) in patients with functional dyspepsia (FD)., Methods: Electronic databases were searched until July 2020 for studies reporting prevalence of SIBO in FD. The prevalence rates, odds ratio, and 95% confidence intervals (CIs) of SIBO in FD and controls were calculated., Results: Seven studies with 263 patients with FD and 84 controls were identified. The odds for SIBO in patients with FD were significantly higher as compared to that in controls (odds ratio = 4.3, 95% CI, 1.1-17.5, 4 studies, 234 participants); however, there was moderate heterogeneity in this analysis. Including high-quality, case-control studies (all using glucose breath tests [GBTs]), the risk of SIBO in patients with FD as compared to controls was 2.8 higher (95% CI 0.8-10.0, 3 studies, 200 participants) with minimal heterogeneity in this analysis. Using the lactulose breath test, SIBO prevalence in FD was significantly higher (53.4%, 95% CI 33.9-71.9, 3 studies, 110 participants) as compared to that with GBT (17.2%, 95% CI 8.6-31.6, 4 studies, 153 participants). Substantial heterogeneity was found in studies using the lactulose breath test but not in studies using GBT. There was no significant difference in SIBO prevalence in patients with FD according to FD subtype., Discussion: This meta-analysis suggests a link between FD and SIBO. The quality of evidence is low and can be largely attributed to the type of breath test for SIBO diagnosis and clinical heterogeneity. More appropriately designed studies are required to confirm the link between SIBO and FD., (Copyright © 2021 by The American College of Gastroenterology.)

Several studies reported a potential role of methane producing archaea in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the prevalence of methane positive small intestinal bacterial overgrowth (SIBO) in IBS and IBD compared with controls. MEDLINE (PubMed) and Embase electronic databases were searched from inception until March 2021 for case-control and prevalence studies reporting SIBO in IBS and IBD. We extracted data from published studies and calculated pooled prevalence of SIBO in IBS or IBD, odds ratios (OR), and 95% CIs, utilizing a random effects model. The final dataset included 17 independent studies assessing the prevalence of methane positive SIBO in 1,653 IBS-patients and 713 controls, and 7 studies assessing the prevalence of methane positive SIBO in 626 IBD-patients and 497 controls, all utilizing breath test for SIBO diagnosis. Prevalence of methane positive SIBO in IBS and IBD was 25.0% (95% CI 18.8-32.4) and 5.6% (95% CI 2.6-11.8), respectively. Methane positive SIBO in IBS was not increased compared to controls (OR = 1.2, 95% CI 0.8-1.7, P = .37) but was significantly more prevalent in IBS-C as compared to IBS-D (OR = 3.1, 95% CI 1.7-5.6, P = .0001). The prevalence of methane-positive SIBO in patients with IBD was 3-fold lower at 7.4% (95% CI 5.4-9.8) compared to 23.5% (95% CI 19.8-27.5) in controls. The prevalence of methane positive SIBO was significantly lower in Crohn's disease as compared to ulcerative colitis, (5.3%, 95% CI 3.0-8.5 vs. 20.2%, 95% CI 12.8-29.4). This systematic review and meta-analysis suggests methane positivity on breath testing is positively associated with IBS-C and inversely with IBD. However, the quality of evidence is low largely due to clinical heterogeneity of the studies. Thus, causality is uncertain and further studies are required.

Introduction: Psychological distress is associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD) but only evidence from prospective longitudinal and treatment studies can indicate whether the link between FGIDs and psychological distress is causal. Emerging evidence suggests underlying biological mechanisms may explain the association of psychological distress with FGIDs., Areas Covered: This review critically evaluates whether anxiety and/or depression and FGIDs are causally related including evidence for a temporal sequence, strength and specificity of the association, biological gradient, and biological plausibility., Expert Opinion: Accumulating evidence suggests that psychological factors are causal for symptoms in a subset of FGID patients and not explained by health care seeking behavior (brain-gut disorder). In other cases, psychological factors may arise secondary to intestinal disease (gut-brain disorder). Prospective population-based studies are needed in FGIDs other than IBS and FD to determine if a similar brain-gut and gut-brain syndrome exists. Treatment studies have not phenotyped FGIDs according to brain-gut versus gut-brain origins which may be important in understanding true treatment efficacy. Future research needs to unravel biological mechanisms that may explain the link between psychological factors and FGIDs but promising data in the area of the brain-gut-immune-microbe axis is emerging.

Background: Small intestinal bacterial overgrowth may play a role in gastrointestinal and non-gastrointestinal diseases., Aims: To use quantitative polymerase chain reaction (qPCR) to determine and compare bacterial loads of duodenal biopsies in asymptomatic controls, and patients with functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). To define effects of gastric acid inhibition on bacterial load, explore links of bacterial load and gastrointestinal symptoms in response to a standardised nutrient challenge and compare bacterial load with glucose breath test results., Methods: In 237 patients (63 controls, 84 FGID and 90 IBD), we collected mucosal samples under aseptic conditions during endoscopy extracted and total DNA. Bacterial load metric was calculated utilising qPCR measurements of the bacterial 16S rRNA gene, normalised to human beta-actin expression. Standard glucose breath test and nutrient challenge test were performed., Results: The duodenal microbial load was higher in patients with FGID (0.22 ± 0.03) than controls (0.07 ± 0.05; P = 0.007) and patients with UC (0.01 ± 0.05) or CD (0.02 ± 0.09), (P = 0.0001). While patients treated with proton pump inhibitors (PPI) had significantly higher bacterial loads than non-users (P < 0.05), this did not explain differences between patient groups and controls. Bacterial load was significantly (r = 0.21, P < 0.016) associated with the symptom response to standardised nutrient challenge test. Methane, but not hydrogen values on glucose breath test were associated with bacterial load measured utilising qPCR., Conclusions: Utilising qPCR, a diagnosis of FGID and treatment with PPI were independently associated with increased bacterial loads. Increased bacterial loads are associated with an augmented symptom response to a standardised nutrient challenge., (© 2020 John Wiley & Sons Ltd.)

Introduction: We conducted a systematic review and meta-analysis to compare the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) and controls., Methods: Electronic databases were searched up to December 2018 for studies reporting SIBO prevalence in patients with IBS. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with IBS and controls were calculated., Results: We included 25 studies with 3,192 patients with IBS and 3,320 controls. SIBO prevalence in patients with IBS was significantly increased compared with controls (OR = 3.7, 95% CI 2.3-6.0). In studies using only healthy controls, the OR for SIBO in patients with IBS was 4.9 (95% CI 2.8-8.6). With breath testing, SIBO prevalence in patients with IBS was 35.5% (95% CI 33.6-37.4) vs 29.7% (95% CI 27.6-31.8) in controls. Culture-based studies yielded a SIBO prevalence of 13.9% (95% CI 11.5-16.4) in patients with IBS and 5.0% (95% CI 3.9-6.2) in controls with a cutoff value of 10 colony-forming units per milliliter vs 33.5% (95% CI 30.1-36.9) in patients with IBS and 8.2% (95% CI 6.8-9.6) in controls with a cutoff value of 10 colony-forming unit per milliliter, respectively. SIBO prevalence diagnosed by lactulose breath test is much greater in both patients with IBS (3.6-fold) and controls (7.6-fold) compared with glucose breath test. Similar difference is seen when lactulose breath test is compared with culture methods. OR for SIBO in patients with IBS-diarrhea compared with IBS-constipation was 1.86 (95% CI 1.83-2.8). Methane-positive breath tests were significantly more prevalent in IBS-constipation compared with IBS-diarrhea (OR = 2.3, 95% CI 1.2-4.2). In patients with IBS, proton pump inhibitor was not associated with SIBO (OR = 0.8, 95% CI 0.5-1.5, P = 0.55)., Discussion: This systematic review and meta-analysis suggests a link between IBS and SIBO. However, the overall quality of the evidence is low. This is mainly due to substantial "clinical heterogeneity" due to lack of uniform selection criteria for cases and controls and limited sensitivity and specificity of the available diagnostic tests.

Goal: The aim of this analysis was to assess in patients with inflammatory bowel disease (IBD) the risk of celiac disease and in celiac disease patients the risk of IBD., Background: Previous studies report a possible association between IBD and celiac disease; however, this link is controversial., Study: Using the search terms "inflammatory bowel disease" and "celiac disease," we identified initially 1525 publications. In total 27 studies met inclusion criteria. Proportions and 95% confidence intervals (CIs) for the prevalence of IBD in celiac disease and vice versa were compared with published prevalence rates for the respective geographic regions., Results: We included 41,482 adult IBD patients (20,357 with Crohn's disease; 19,791 with ulcerative colitis; and 459 patients with celiac disease). Overall, in IBD patients the prevalence of celiac disease was 1110/100,000 (95% CI, 1010-1210/100,000) as compared with a prevalence of 620/100,000 (95% CI, 610-630/100,000) in the respective populations (odds ratio, 2.23; 95% CI, 1.99-2.50). In contrast, in patients with celiac disease, 2130/100,000 had IBD (95% CI, 1590-2670/100,000) as compared with 260/100,000 (95% CI, 250/100,000-270/100,000) in the respective populations (odds ratio, 11.10; 95% CI, 8.55-14.40). This effect was not different for ulcerative colitis and Crohn's disease. Although there was no evidence for publication bias for celiac disease in IBD, the funnel plot suggested that the association between IBD in celiac disease might be influenced by publication bias., Conclusions: The data are consistent with the notion that celiac disease is a risk factor for IBD and to lesser degree patients with IBD have an increased risk of celiac disease.

Background: The pathogenesis of functional GI disorders (FGIDs) is uncertain. However, underlying immune activation and psychological distress has been documented in irritable bowel syndrome (IBS) and functional dyspepsia (FD). Epidemiological data from the UK suggest that FGIDs are linked to atopy and certain autoimmune diseases but this has not been confirmed., Aim: To test if allergic or autoimmune diseases are independently associated with FGIDs, irrespective of psychological distress in a large population based study., Methods: A total of 3542 people (mean age 57.9 years and 52.7% females) randomly selected from the Australian population, returned a mail survey (response rate = 43%). The survey asked about a physician diagnosis of autoimmune disease (scleroderma, psoriasis, rheumatoid arthritis and diabetes mellitus) or allergic conditions (asthma, food, pollen and/or animal allergy). The questionnaire assessed psychological distress and Rome III criteria for FD and IBS., Results: Asthma, food, pollen and animal allergies, psoriasis and rheumatoid arthritis were univariately significantly associated with IBS and FD. Food allergy (OR = 1.66; 95% CI = 1.15-2.40, P = 0.007), psoriasis (OR = 1.81; 95% CI = 1.19-2.74, P = 0.006) and rheumatoid arthritis (OR = 1.68; 95% CI = 1.15-2.4, P = 0.007) were independent risk factors for IBS, controlling for age, gender and psychological distress. In FD, asthma (OR = 1.32; 95% CI = 1.04-1.68, P = 0.025) and food allergy (OR = 1.78; 95% CI = 1.28-2.49, P = 0.001) were independent predictors, controlling for age, sex and psychological distress., Conclusions: There is evidence that both atopic and autoimmune diseases are risk factors for FGIDs, independent of psychological distress, differing in IBS and FD. This provides evidence that different peripheral pathways may be involved in the pathogenesis of certain FGIDs., (© 2019 John Wiley & Sons Ltd.)

Background: Current data on small intestinal bacterial overgrowth (SIBO) in patients with inflammatory bowel diseases (IBD) are controversial., Aim: To conduct a systematic review and meta-analysis to determine the prevalence of SIBO in patients with ulcerative colitis (UC) and Crohn's disease (CD)., Methods: Electronic databases were searched up to May 2018 for studies reporting prevalence of SIBO in IBD patients. The prevalence rate of SIBO among IBD patients and the odds ratio (OR) and 95% CI of SIBO in IBD patients compared with controls were calculated., Results: The final dataset included 11 studies (1175 adult patients with IBD and 407 controls), all utilising breath test for diagnosis of SIBO. The proportion of SIBO in IBD patients was 22.3% (95% CI 19.92-24.68). The OR for SIBO in IBD patients was 9.51 (95% CI 3.39-26.68) compared to non-IBD controls, and high in both CD (OR = 10.86; 95% CI 2.76-42.69) and UC (OR = 7.96; 95% CI 1.66-38.35). In patients with CD, subgroup analysis showed the presence of fibrostenosing disease (OR = 7.47; 95% CI 2.51-22.20) and prior bowel surgery (OR = 2.38; 95% CI 1.65-3.44), especially resection of the ileocecal valve, increased the odds of SIBO. Individual studies suggest that combined small and large bowel disease but not disease activity may be associated with SIBO., Conclusions: Overall, there is a substantial increase in the prevalence of SIBO in IBD patients compared to controls. Prior surgery and the presence of fibrostenosing disease are risk factors for SIBO in IBD., (© 2019 John Wiley & Sons Ltd.)

Background: According to Rome IV criteria, functional dyspepsia (FD) and irritable bowel syndrome (IBS) are distinct functional gastrointestinal disorders (FGID); however, overlap of these conditions is common in population-based studies, but clinical data are lacking., Aims: To determine the overlap of FD and IBS in the clinical setting and define risk factors for the overlap of FD/IBS., Methods: A total of 1127 consecutive gastroenterology outpatients of a tertiary center were recruited and symptoms assessed with a standardized validated questionnaire. Patients without evidence for structural or biochemical abnormalities as a cause of symptoms were then categorized based upon the symptom pattern as having FD, IBS or FD/IBS overlap. Additionally, this categorization was compared with the clinical diagnosis documented in the integrated electronic medical records system., Results: A total of 120 patients had a clinical diagnosis of a FGID. Based upon standardized assessment with a questionnaire, 64% of patients had FD/IBS overlap as compared to 23% based upon the routine clinical documentation. In patients with severe IBS or FD symptoms (defined as symptoms affecting quality of life), the likelihood of FD/IBS overlap was substantially increased (OR = 3.1; 95%CI 1.9-5.0) and (OR = 9.0; 95%CI 3.5-22.7), respectively. Thus, symptom severity for IBS- or FD symptoms were significantly higher for patients with FD/IBS overlap as compared to patients with FD or IBS alone (p all < 0.01). Age, gender and IBS-subtype were not associated with overlap., Conclusion: In the clinical setting, overlap of FD and IBS is the norm rather than the exception. FD/IBS overlap is associated with a more severe manifestation of a FGID.

Background: Cigarette smoking is a known risk factor in a number of gastrointestinal (GI) diseases in which the microbiota is implicated, including duodenal ulcer and Crohn's disease. Smoking has the potential to alter the microbiota; however, to date, the impact of smoking on the mucosa-associated microbiota (MAM), and particularly that of the upper GI tract, remains very poorly characterised. Thus, we investigated the impact of smoking on the upper small intestinal MAM. A total of 102 patients undergoing upper GI endoscopy for the assessment of GI symptoms, iron deficiency, or Crohn's disease, but without identifiable lesions in the duodenum, were recruited. Smoking status was determined during clinical assessment and patients classified as current (n = 21), previous smokers (n = 40), or having never smoked (n = 41). The duodenal (D2) MAM was profiled via 16S rRNA gene amplicon sequencing., Results: Smoking, both current and previous, is associated with significantly reduced bacterial diversity in the upper small intestinal mucosa, as compared to patients who had never smoked. This was accompanied by higher relative abundance of Firmicutes, specifically Streptococcus and Veillonella spp. The relative abundance of the genus Rothia was also observed to be greater in current smokers; while in contrast, levels of Prevotella and Neisseria were lower. The MAM profiles and diversity of previous smokers were observed to be intermediate between current and never smokers. Smoking did not impact the total density of bacteria present on the mucosa., Conclusions: These data indicate the duodenal MAM of current smokers is characterised by reduced bacterial diversity, which is partially but not completely restored in previous smokers. While the precise mechanisms remain to be elucidated, these microbiota changes may in some part explain the adverse effects of smoking on mucosa-associated diseases of the GI tract. Smoking status requires consideration when interpreting MAM data.

Background and Aim: A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D., Methods: Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of < 100 mcg/g stool represented severe and < 200 mcg/g mild to moderate PEI. Patients whose fecal elastase was < 200 mcg/g underwent testing for pancreatic pathology with an endoscopic ultrasound or abdominal CT., Results: Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis., Conclusion: One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Functional dyspepsia (FD) is a very common condition affecting more than 10% of the population. While there is no cure, a few drugs have been found to be effective for the relief of symptoms, although most are only effective in a subgroup of patients. We assess and compare the efficacy of a fixed peppermint/caraway-oil-combination (Menthacarin) on symptoms and quality of life (QoL) in patients with FD symptoms consistent with epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS)., Methods: In a prospective, double-blind, multicenter trial, 114 outpatients with chronic or recurrent FD were randomized and treated for 4 weeks with the proprietary peppermint- and caraway-oil-preparation Menthacarin or placebo (2×1 capsule/day). Improvement of abdominal pain and discomfort were used as co-primary efficacy measures (scores measured with the validated Nepean Dyspepsia Index)., Key Results: After 2 and 4 weeks, active treatment was superior to placebo in alleviating symptoms consistent with PDS and EPS (P all <.001). After 4 weeks of treatment, pain and discomfort scores improved by 7.6±4.8 and 3.6±2.5 points (full analysis set; mean±SD) for Menthacarin and by 3.4±4.3 and 1.3±2.1 points for placebo, respectively. All secondary efficacy measures showed advantages for Menthacarin., Conclusions & Inferences: Menthacarin is an effective therapy for the relief of pain and discomfort and improvement of disease-specific QoL in patients with FD and significantly improves symptoms consistent with EPS and PDS., (© 2017 John Wiley & Sons Ltd.)

Introduction: Case control studies suggest an inverse association between Helicobacter pylori (H. pylori) and Crohn's disease (CD). It is possible this could be accounted for by confounders such as antibiotic therapy. Analyzing the geographic distribution of H. pylori and the links with the incidence and prevalence of CD would be an alternative approach to circumvent these confounders., Methods: The literature was searched for studies published between 1990 and 2016 that reported incidence or prevalence data for CD in random population samples in developed countries (GDP per capita >20,000 USD/year). Corresponding prevalence studies for H. pylori in these same regions were then sought matched to the same time period (±6 years). The association between the incidence and prevalence of CD and H. pylori prevalence rates were assessed before and after adjusting for GDP and life expectancy., Results: A total of 19 CD prevalence and 22 CD incidence studies from 10 European countries, Japan, USA, and Australia with date-matched H. pylori prevalence data were identified. The mean H. pylori prevalence rate was 43.4% (range 15.5-85%), and the mean rates for incidence and prevalence for CD were 6.9 and 91.0/100,000 respectively. The incidence (r = -0.469, p < 0.03) and prevalence (r = -0.527, p = 0.02) of CD was inversely and significantly associated with prevalence of H. pylori infection., Conclusions: Our data demonstrate a significant inverse association between geographic distribution of H. pylori and CD. Thus, it is highly unlikely that the findings of previous case control studies were simply due to confounding factors such as concomitant antibiotic use in CD patients.

Background: The clinical assessments of patients with gastrointestinal symptoms can be time-consuming, and the symptoms captured during the consultation may be influenced by a variety of patient and non-patient factors. To facilitate standardized symptom assessment in the routine clinical setting, we developed the Structured Assessment of Gastrointestinal Symptom (SAGIS) instrument to precisely characterize symptoms in a routine clinical setting., Aims: We aimed to validate SAGIS including its reliability, construct and discriminant validity, and utility in the clinical setting., Methods: Development of the SAGIS consisted of initial interviews with patients referred for the diagnostic work-up of digestive symptoms and relevant complaints identified. The final instrument consisted of 22 items as well as questions on extra intestinal symptoms and was given to 1120 consecutive patients attending a gastroenterology clinic randomly split into derivation (n = 596) and validation datasets (n = 551). Discriminant validity along with test-retest reliability was assessed. The time taken to perform a clinical assessment with and without the SAGIS was recorded along with doctor satisfaction with this tool., Results: Exploratory factor analysis conducted on the derivation sample suggested five symptom constructs labeled as abdominal pain/discomfort (seven items), gastroesophageal reflux disease/regurgitation symptoms (four items), nausea/vomiting (three items), diarrhea/incontinence (five items), and difficult defecation and constipation (2 items). Confirmatory factor analysis conducted on the validation sample supported the initially developed five-factor measurement model ([Formula: see text], p < 0.0001, χ 2 /df = 4.6, CFI = 0.90, TLI = 0.88, RMSEA = 0.08). All symptom groups demonstrated differentiation between disease groups. The SAGIS was shown to be reliable over time and resulted in a 38% reduction of the time required for clinical assessment., Conclusions: The SAGIS instrument has excellent psychometric properties and supports the clinical assessment of and symptom-based categorization of patients with a wide spectrum of gastrointestinal symptoms.

Background: Traditionally, functional gastrointestinal disorders (FGIDs) are conceptualised as originating in the brain via stress pathways (brain-to-gut). It is uncertain how many with irritable bowel syndrome (IBS) and functional dyspepsia (FD) have a gut origin of symptoms (gut-to-brain pathway)., Aims: To determine if there is a distinct brain-to-gut FGID (where psychological symptoms begin first) and separately a distinct gut-to-brain FGID (where gut symptoms start first)., Methods: A prospective random population sample from Newcastle, Australia who responded to a validated survey in 2012 and completed a 1-year follow-up survey (n = 1900). The surveys contained questions on Rome III IBS and FD and the Hospital Anxiety and Depression Scale., Results: We found that higher levels of anxiety and depression at baseline were significant predictors of developing IBS (OR = 1.31; 95% CI 1.06-1.61, P = 0.01; OR = 1.54; 95% CI 1.29-1.83, P < 0.001) and FD (OR = 1.28; 95% CI 1.05-1.55, P = 0.01; OR = 1.55, 95% CI 1.32-1.83, P < 0.001), respectively, at the 1-year follow-up. Among those people who did not have elevated levels of anxiety and depression at baseline, subjects at baseline with documented IBS (mean difference 0.34; 95% CI 0.13-0.55, P = 0.002; 0.81; 95% CI 0.47-1.15, P < 0.001) and FD (0.38; 95% CI 0.14-0.63, P = 0.002; 0.92; 95% CI 0.57-1.27, P < 0.001), reported significantly higher levels of anxiety and depression at the 1-year follow-up. We calculated in one-third of individuals a mood disorder precedes FGID but in two-thirds an FGID precedes the mood disorder., Conclusion: While brain-gut pathways are bidirectional, a major subset begin with gut symptoms first and only then psychological distress develops, implicating primary gut mechanisms as drivers of the gut and extra-intestinal features in many cases., (© 2016 John Wiley & Sons Ltd.)

Background: Abdominal migraine (AM) is a syndrome usually recognised in childhood. The syndrome is characterised by episodic attacks of severe abdominal pain and vasomotor symptoms, nausea and vomiting. It is a poorly understood disorder largely due to a limited recognition of this condition by the medical community. However, the publication of AM diagnostic guidelines by the International Headache Society a decade ago and the recognition of AM in the Rome Classification of functional gastrointestinal disorders have helped to legitimise this disorder and facilitate research., Overview: AM is relatively common, affecting up to 4% of the paediatric population. Whilst AM is not believed to continue into adulthood for the majority of children, it has the propensity to develop into probable migraine and recurrent abdominal pain in adulthood. The pathophysiology of this condition remains unclear and as a result treatment for this condition is suboptimal with avoidance of triggers and prophylactic treatment currently recommended when an episode begins., Conclusion: The recognition of AM by the IHS and the Rome Foundation should help facilitate future research into the pathophysiology of this debilitating condition and as a result better treatments for AM should emerge. Randomised controlled trials should be a priority., (© International Headache Society 2015.)

Functional dyspepsia is relatively common yet poorly understood. The best accepted diagnostic criteria are the Rome III criteria. The epidemiology, healthcare seeking rates, impact and pathophysiology are reviewed with a focus on women. Treatment is limited with no clearly established regimen currently recommended. Duodenal eosinophilia may be found in a subset. Proton pump inhibitors and prokinetic agents represent the standard therapeutic regimen after Helicobacter pylori infection has been eliminated. Some novel agents such as the prokinetic acotiamide appear promising; however, the need for a safe and efficacious treatment remains largely unmet. This review also describes the currently available management options for functional dyspepsia.

Background: The role of childhood environment including exposure to infection via siblings and pets in irritable bowel syndrome (IBS) and dyspepsia is relatively unknown. We assessed proxy measures of microbial exposure in early childhood to assess if these are associated with IBS and functional dyspepsia in later life., Methods: Participants (n = 767, response rate = 53%) were a random population sample from Sydney, Australia who previously responded to a validated survey. IBS and functional dyspepsia were defined using Rome III criteria. Early environmental risk factors assessed included type of birth delivery, premature birth, breastfeeding, bedroom sharing, and pet exposure (the latter two then combined as early hygiene factors) up to 5 years of age. Post infectious IBS (PI-IBS) was assessed by development of IBS following gastroenteritis., Key Results: In this sample, in adult life 17% developed IBS (of which 20% had PI-IBS) and 12% functional dyspepsia. Development of IBS was associated with childhood factors-a shorter duration of breastfeeding (odds ratios [OR] = 0.87, 95% CI: 0.78-0.97, p = 0.01), sharing a bedroom (OR = 1.89, 95% CI: 1.73-3.08, p = 0.01), exposure to a herbivore pet (OR = 1.65 (1.10, 2.48), p = 0.02), and hygiene factors (OR = 4.39; 95% CI: 1.89-10.21, p = 0.001). The sole factor associated with functional dyspepsia was exposure to a herbivore pet (1.79; 95% CI: 1.19-2.87, p = 0.02)., Conclusions & Inferences: Childhood environment factors, particularly bedroom sharing and pet exposure, combined with subsequent risk of microbial exposure are a risk factor for IBS in later life. These associations however need confirmation to rule out any risk of a type I error., (© 2015 John Wiley & Sons Ltd.)

Background: While the Rome III classification recognises functional constipation (FC) and constipation predominant IBS (IBS-C) as distinct disorders, recent evidence has suggested that these disorders are difficult to separate in clinical practice., Aim: To identify whether clinical and lifestyle factors differentiate Rome III-defined IBS-C from FC based on gastrointestinal symptoms and lifestyle characteristics., Method: 3260 people randomly selected from the Australian population returned a postal survey. FC and IBS-C were defined according to Rome III. The first model used logistic regression to differentiate IBS-C from FC based on lifestyle, quality-of-life and psychological characteristics. The second approach was data-driven employing latent class analysis (LCA) to identify naturally occurring clusters in the data considering all symptoms involved in the Rome III criteria for IBS-C and FC., Results: We found n = 206 (6.5%; 95% CI 5.7-7.4%) people met strict Rome III FC whereas n = 109 (3.5%; 95% CI 2.8-4.1%) met strict Rome III IBS-C. The case-control approach indicated that FC patients reported an older age at onset of constipation, were less likely to exercise, had higher mental QoL and less health care seeking than IBS-C. LCA yielded one latent class that was predominantly (75%) FC, while the other class was approximately half IBS-C and half FC. The FC-dominated latent class had clearly lower levels of symptoms used to classify IBS (pain-related symptoms) and was more likely to be male (P = 0.046) but was otherwise similar in distribution of lifestyle factors to the mixed class., Conclusion: The latent class analysis approach suggests a differentiation based more on symptom severity rather than the Rome III view., (© 2015 John Wiley & Sons Ltd.)

Objective: Functional gastrointestinal disorders (FGID) have been shown to be associated with both comorbid mood disorders and traumatic events such as abuse earlier in life. In a longitudinal study, we tested a model that hypothesized: (i) childhood abuse was associated with subsequent mood disorder and pain or interference in life by bowel symptoms both directly and indirectly via neurotic personality; and (ii) an ongoing cycle of mood disorder impacts on bowel symptoms., Design: Subjects from the general population classified as irritable bowel syndrome and/or functional dyspepsia (IBS/FD, n = 207) or free of FGID (n = 100) were prospectively studied every 6 months over 18 months. In addition to bowel symptom interference and abdominal pain, measures of personality (neuroticism), childhood abuse history, depression, and anxiety were obtained. The hypothesized model was tested via Path Modelling., Results: Childhood abuse was found to be directly associated with neuroticism but only indirectly associated with baseline interference and mood disorders (via neuroticism). The data further supported an ongoing cycle of elevations in mood disorders and pain/interference by bowel symptoms. The data supported direct effects of interference at one time point on interference at the subsequent time point in addition to indirect effects of prior anxiety and depression. Repeating the model with pain frequency as the outcome yielded almost identical findings which suggests the findings are generalized across domains of symptoms and quality-of-life., Conclusion: Our data provide support for a model characterized by a 'vicious circle' between mood disorders and FGID symptoms in adulthood, with initial input from early life factors.

Objectives: Very little is known about whether the reported health-related impact of constipation is worse in people who experience constipation over a long period of time vs. those with more transient symptoms. We aimed to determine the impact of persistent vs. transient constipation on health-related quality of life (QOL), depression, and mortality., Methods: We analyzed data from 5,107 women (aged 70-75 years in 1996) who answered "Have you had constipation in the past 12 months?" in all five surveys sent out every 3 years of the Australian Longitudinal Study on Women's Health., Results: Of the 5,107 women, 20.9, 54.1, and 24.7% reported having persistent constipation on at least 4 out of 5 surveys, transient constipation reported on 1-3 surveys, or none reported over the 15-year time frame, respectively. Women who reported persistent constipation had significantly lower scores for all domains of QOL on the SF-36 except role-emotional, and had higher levels of self-reported depression, even after adjusting for number of chronic illnesses and fluid intake. Mortality rates were increased when comparing women with no reported constipation with persistently reported constipation (8.2% vs. 11%, odds ratio = 1.32, 95% confidence interval 1.0, 1.74, P = 0.05) controlling for specific chronic illnesses., Conclusions: Persistent constipation among older women is associated with poor health outcomes.

Objectives: We aim to evaluate the psychological impact and risk factors associated with new onset FI over 12 years in adults over 18 years for the first time in a population-based study., Methods: Participants (n = 1775) were a random population sample from Penrith, Australia who responded to a survey in 1997 and completed a 12-year follow-up survey (response rate = 60%). FI was defined as having leakage of stool over the past 12 months. The original and follow-up surveys contained valid questions on demographic, gastrointestinal and psychological symptoms., Results: 114 (11.4%) reported new onset FI at the 12 year follow-up. People who reported FI at the 12 year follow-up were significantly more anxious and depressed. In terms of baseline risk factors only bloating (OR = 1.3; 95%CI 1.0-1.6, P = 0.026) was an independent predictor of developing new onset FI. However, current bowel symptoms measured at follow-up including less likelihood of <3 bowel motions a week, increased urgency and mucus were independently associated with having FI at follow-up., Conclusion: FI is associated with anxiety and depression. Baseline GI symptoms do not appear to be as important as current bowel symptoms in determining who develops FI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain-gut mechanism in FGIDs., Design: Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up., Results: Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up., Conclusions: The central nervous system and gut interact bidirectionally in FGIDs.

Objective: A single previous paper on this topic found a direct pathway between cognitive behavioral therapy (CBT) and an irritable bowel syndrome (IBS) global symptom score. This is controversial since under the biopsychosocial model, the expectation is that CBT's effect would be mediated by mood. Using more sensitive bowel symptom scales and measurements at additional time points, we aimed to compare the relative strengths of direct pathways between CBT and change in IBS symptoms and indirect pathways that operate via mood state using structural equation modeling., Methods: Our data set included 105 people with Rome I IBS randomized to individual CBT (n=34), relaxation therapy (n=36), and usual medical care (n=35). The primary outcome was defined as adequate relief of IBS symptoms in terms of the distress, frequency, and impairment according to the Bowel Symptom Severity Scale. Outcomes in functional status (according to the 36-item Short-Form Health Survey) and psychological status (Hospital Anxiety and Depression Scale) were secondary outcomes., Results: Our data suggest indirect pathways that operate via mood, most clearly anxiety but to a lesser extent depression. Statistically significant pathways were identified that lead from CBT to change in mood state thence to change in bowel symptoms, followed by further changes in mood then changes in bowel symptoms. Our data provide no evidence of direct effect of CBT on bowel symptoms., Conclusions: The present study suggests that CBT may operate via changes in mood state while not ruling out the possibility of direct effects. Our findings do not directly support, but are consistent with, a biopsychosocial model., (Copyright © 2011. Published by Elsevier Inc.)

Background: Anxiety symptoms and anxiety disorders are highly prevalent among elderly people, although infrequently the subject of systematic research in this age group. One important limitation is the lack of a widely accepted instrument to measure dimensional anxiety in both normal old people and old people with mental health problems seen in various settings. Accordingly, we developed and tested of a short scale to measure anxiety in older people., Methods: We generated a large number of potential items de novo and by reference to existing anxiety scales, and then reduced the number of items to 60 through consultation with a reference group consisting of psychologists, psychiatrists and normal elderly people. We then tested the psychometric properties of these 60 items in 452 normal old people and 46 patients attending a psychogeriatric service. We were able to reduce the number of items to 20. We chose a 1-week perspective and a dichotomous response scale., Results: Cronbach's alpha for the 20-item Geriatric Anxiety Inventory (GAI) was 0.91 among normal elderly people and 0.93 in the psychogeriatric sample. Concurrent validity with a variety of other measures was demonstrated in both the normal sample and the psychogeriatric sample. Inter-rater and test-retest reliability were found to be excellent. Receiver operating characteristic analysis indicated a cut-point of 10/11 for the detection of DSM-IV Generalized Anxiety Disorder (GAD) in the psychogeriatric sample, with 83% of patients correctly classified with a specificity of 84% and a sensitivity of 75%., Conclusions: The GAI is a new 20-item self-report or nurse-administered scale that measures dimensional anxiety in elderly people. It has sound psychometric properties. Initial clinical testing indicates that it is able to discriminate between those with and without any anxiety disorder and between those with and without DSM-IV GAD.

Background: Population-based studies of the prevalence of all functional gastrointestinal disorders (FGID) using the Rome II criteria are lacking. It is also not certain whether subjects who meet the Rome II criteria for an FGID are different in terms of demographic and psychological characteristics from those subjects meeting exclusively the more restrictive Rome I criteria., Aim: To determine whether using the more restrictive Rome I criteria would result in a more biologically determined group of FGID than when the Rome II is applied., Methods: Subjects included individuals aged 18 years and older (n = 1,225) from the Penrith population who were initially surveyed with the Penrith District Health Survey in 1997. Subjects were sent a self-report questionnaire that contained items on gastrointestinal symptoms applying the Rome II criteria. Subjects were also assessed on psychological and personality factors and on physical and mental functioning., Results: A total of 36.1% (n = 275) of respondents was diagnosed with an FGID according to Rome II criteria. The five most prevalent FGID were functional heartburn (10.4%), irritable bowel syndrome (8.9%), functional incontinence (7.6%), proctalgia fugax (6.5%) and functional chest pain (5.1%). Subjects meeting Rome II only criteria for FGID scored significantly higher on measures of psychological caseness and emotionality than Rome I only subjects, and these were independently associated with meeting Rome I only versus Rome II only criteria for FGID., Conclusion: The Rome II criteria FGID are common and do not appear to identify a vastly different group of FGID sufferers compared with the earlier Rome I criteria.

Background: The drivers of conventional and, especially, alternative health care use for irritable bowel syndrome and functional dyspepsia are not clear., Aim: To determine the predictors of conventional and alternative health care use for irritable bowel syndrome and functional dyspepsia., Methods: Two hundred and seven subjects with irritable bowel syndrome or functional dyspepsia, identified from a previous population survey, were included in the study. Individuals with irritable bowel syndrome/functional dyspepsia were defined as consulters (n = 103) if they had visited their doctor for gastrointestinal symptoms more than once in the past year. Controls (n = 100) did not report having any abdominal pain. Subjects were given structured interviews to assess the Diagnostic and Statistical Manual - version IV (DSM-IV) and International Classification of Disorders - version 10 (ICD-10) psychiatric diagnosis for anxiety, depression, somatization or any psychiatric diagnosis, aspects of health care use and symptom factors., Results: About one-half (n = 103, 49.8%) of community subjects with irritable bowel syndrome/functional dyspepsia had sought conventional care for gastrointestinal symptoms in the past 12 months. Lifetime rates for alternative health care use for gastrointestinal symptoms were 20.8% (n = 43). Independent predictors of conventional health care use were more frequent abdominal pain, greater interference of gastrointestinal symptoms with work and activities and a greater satisfaction with the physician-patient relationship. Being female independently predicted alternative health care use., Conclusions: Psychological morbidity did not predict conventional or alternative health care use for gastrointestinal symptoms. Other factors were more important.

Objectives: Health care use is a costly outcome of the irritable bowel syndrome (IBS) and nonulcer dyspepsia (NUD), but the predictors of this behavior remain poorly defined. We aimed to systematically review the literature to determine which symptoms and psychosocial factors drive health care seeking in these disorders., Methods: A broad based MEDLINE and Current Contents search between 1966 and 2000 identified 44 relevant publications. References from these articles were also reviewed., Results: The literature suggests that symptom severity is an important factor, but only explains a small proportion of the health care seeking behavior associated with these disorders in population-based studies. Psychosocial factors including life event stress, psychological morbidity, personality, abuse and abnormal illness attitudes and beliefs have been found to characterize those that seek help versus those that do not. The role of other psychosocial factors such as social support, coping style and knowledge about illness are as yet undetermined., Conclusions: A model for health care seeking for IBS and NUD, with an emphasis on psychosocial factors is presented, but remains to be tested.