A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis.

INTRODUCTION: Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. METHODS: General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. RESULTS: Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). DISCUSSION: Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.

Prevalence of small intestinal bacterial overgrowth in intestinal failure syndrome: A systematic review and meta-analysis.

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 (I2 = 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.

Healthcare Utilization Patterns: Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Gastroesophageal Reflux Disease.

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.

Social determinants and participation in fecal occult blood test based colorectal cancer screening: A qualitative systematic review and meta-synthesis.

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.

Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia.

OBJECTIVE: Functional dyspepsia (FD) is a complex disorder, with debilitating epigastric symptoms. Evidence suggests alterations in gastrointestinal (GI) motility, visceral hypersensitivity, permeability and low-level immune activation in the duodenum may play a role. However, we still have a relatively poor understanding of how these factors interact to precipitate the onset of FD symptoms which are frequently meal related. The duodenal microbiota, in combination with specific dietary substrates, may be important mediators in disease pathophysiology; however, these interlinked factors have not been thoroughly investigated in FD. DESIGN: Eighty-six individuals (56 FD, 30 controls) undergoing endoscopy were consecutively recruited and underwent detailed clinical assessment, including upper GI symptoms, gastric emptying and dietary assessment. Duodenal biopsies were obtained aseptically, and the mucosa-associated microbiota (MAM) analysed via 16S rRNA gene amplicon sequencing. RESULTS: The relative abundances of predominant members of the Firmicutes, Bacteroidota and Fusobacteriota phyla were linked to symptom burden in FD. Inverse relationships between the relative abundances of Streptococcus and Prevotella, and the relative abundance of Veillonella spp with gastric emptying time, were also observed. No significant differences in long-term nutrient intake or diet quality were found between FD and controls, and there appeared to be limited association between habitual diet and duodenal MAM profiles. CONCLUSION: This study suggests a link between the duodenal MAM, gastric emptying and FD symptoms, and this is largely independent of long-term dietary intake.

Upper GI endoscopy in subjects with positive fecal occult blood test undergoing colonoscopy: systematic review and meta-analysis.

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.

Development and Validation of a Patient-Reported Experience Measure for Gastrointestinal Endoscopy: The Comprehensive Endoscopy Satisfaction Tool (CEST).

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.

Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies.

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 (I2 = 93.61, P = .0001; and I2 = 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.

Utilising lipid and, arginine and proline metabolism in blood plasma to differentiate the biochemical expression in functional dyspepsia (FD) and irritable bowel syndrome (IBS).

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-3ß-ol, 3-O-ß-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.

Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.

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.

Concomitant Irritable Bowel Syndrome Does Not Influence the Response to Antimicrobial Therapy in Patients with Functional Dyspepsia.

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.

Evaluation of a Multidisciplinary Integrated Treatment Approach Versus Standard Model of Care for Functional Gastrointestinal Disorders (FGIDS): A Matched Cohort Study.

BACKGROUND: Functional gastrointestinal disorders (FGID) are linked to a variety of potential causes, and treatments include reassurance, life-style (including diet), psychological, or pharmacologic interventions. AIMS: To assess whether a multidisciplinary integrated treatment approach delivered in a dedicated integrated care clinic (ICC) was superior to the standard model of care in relation to the gastrointestinal symptom burden. METHODS: A matched cohort of 52 consecutive patients with severe manifestation of FGID were matched with 104 control patients based upon diagnosis, gender, age, and symptom severity. Patients in the ICC received structured assessment and 12-weeks integrated treatment sessions provided as required by gastroenterologist and allied health team. Control patients received standard medical care at the same tertiary center with access to allied health services as required but no standardized interprofessional team approach. Primary outcome was reduction in gastrointestinal symptom burden as measured by the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS). Secondary outcome was reduction in anxiety and depressive symptoms as measured by the Hospital Anxiety and Depression Scale (HADS). RESULTS: Mixed models estimated the within ICC change in SAGIS total as -9.7 (95% CI -13.6, -5.8; p < 0.0001), compared with -1.7 (95% CI -4.0, 0.6; p = 0.15) for controls. The difference between groups reached statistical significance, -7.6 (95% CI -11.4, -3.8; p < 0.0001). Total HADS scores in ICC patients were 3.4 points lower post-intervention and reached statistical significance (p = 0.001). CONCLUSION: This matched cohort study demonstrates superior short-term outcomes of FGID patients in a structured multidisciplinary care setting as compared to standard care.

Small Intestinal Bacterial Overgrowth in Functional Dyspepsia: A Systematic Review and Meta-Analysis.

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.

Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Case-Control Studies.

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.

Incidence and prevalence of self-reported non-coeliac wheat sensitivity and gluten avoidance in Australia.

OBJECTIVES: To determine the incidence of self-reported non-coeliac wheat sensitivity (SR-NCWS) and factors associated with its onset and resolution; to describe the prevalence of factors associated with gluten avoidance. DESIGN: Longitudinal cohort study; analysis of responses to self-administered validated questionnaires (Digestive Health and Wellbeing surveys, 2015 and 2018). SETTING, PARTICIPANTS: Subset of an adult population sample randomly selected in 2015 from the electoral rolls for the Newcastle and Gosford regions of New South Wales. MAIN OUTCOME MEASURES: Prevalence of SR-NCWS (2015, 2018) and incidence and resolution of SR-NCWS, each by demographic and medical factors; prevalence of gluten avoidance and reasons for gluten avoidance (2018). RESULTS: 1322 of 2185 eligible participants completed the 2018 survey (response rate, 60.5%). The prevalence of SR-NCWS was similar in 2015 (13.8%; 95% CI, 12.0-15.8%) and 2018 (13.9%; 95% CI, 12.1-15.9%); 69 of 1301 respondents (5.3%) reported developing new onset (incident) SR-NCWS between 2015 and 2018 (incidence, 1.8% per year). Incident SR-NCWS was significantly associated with a diagnosis of functional dyspepsia, and negatively associated with being male or older. Gluten avoidance was reported in 2018 by 24.2% of respondents (20.5% partial, 3.8% complete avoidance); general health was the most frequent reason for avoidance (168 of 316 avoiders, 53%). All 13 participants with coeliac disease, 56 of 138 with irritable bowel syndrome (41%), and 69 of 237 with functional dyspepsia (29%) avoided dietary gluten. CONCLUSIONS: The prevalence of SR-NCWS was similar in 2015 and 2018. Baseline (2015) and incident SR-NCWS (2018) were each associated with functional gastrointestinal disorders. The number of people avoiding dietary gluten exceeds that of people with coeliac disease or SR-NCWS, and general health considerations and abdominal symptoms are the most frequently reported reasons for avoidance.

Link Between Celiac Disease and Inflammatory Bowel Disease.

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.

Overlap of Irritable Bowel Syndrome and Functional Dyspepsia in the Clinical Setting: Prevalence and Risk Factors.

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.

Wheat Intolerance and Chronic Gastrointestinal Symptoms in an Australian Population-based Study: Association Between Wheat Sensitivity, Celiac Disease and Functional Gastrointestinal Disorders.

OBJECTIVES: Wheat avoidance in the absence of celiac disease (CD) is common but occurrence of concurrent functional gastrointestinal disorders (FGIDs) in this group is uncertain. The aims of this study were to determine the prevalence of self-reported wheat or gluten sensitivity and doctor diagnosed CD in an Australian population, define the associated gastrointestinal (GI) symptoms and FGIDs, and determine the relationship between self-reported wheat sensitivity, demographic and medical factors. METHODS: A total of 3542 people randomly selected from the Australian population returned a mail survey which contained questions on wheat avoidance, GI symptoms, demographic, medical, and lifestyle factors. We defined self-reported wheat sensitivity as people who reported gastrointestinal symptoms on ingestion of wheat based foods, but did not suffer from celiac disease, inflammatory bowel disease or colorectal cancer. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed by Rome III criteria. CD status was self-reported. RESULTS: The prevalence of self-reported wheat sensitivity in this cohort was 14.9% (95% CI 13.7-16.2). The prevalence of CD was 1.2% (95%CI 0.8-1.6). Doctor diagnosed CD was significantly associated with a diagnosis of FD (OR 3.35, 95%CI 1.72-6.52) and IBS (OR 2.28, 95%CI 1.08-4.81). Those with self-reported wheat sensitivity were more likely to report multiple abdominal symptoms (of the 18 assessed) than those without (3.9 symptoms with self-reported wheat sensitivity vs. 1.6 without, p = 0.0001). In a multivariate analysis, self-reported wheat sensitivity was independently associated with IBS (OR 3.55, 95%CI 2.71-4.65) and FD (1.48, 95%CI 1.13-1.94). CONCLUSIONS: Self-reported wheat sensitivity is common, with a prevalence of 14.9% in this cohort. There is a strong association between both celiac disease and self-reported wheat sensitivity, and chronic gastrointestinal symptoms, as well as a diagnosis of FD and IBS.

Mood and Anxiety Disorders Precede Development of Functional Gastrointestinal Disorders in Patients but Not in the Population.

BACKGROUND & AIMS: Understanding the interactions between brain and gastrointestinal disorders requires analysis of the order of disease onset. We analyzed data from 2 independent studies to determine the proportion of individuals with diagnoses of functional gastrointestinal disorders (FGIDs) before diagnoses of mood or anxiety disorders (gut to brain), and vice versa (brain to gut). METHODS: We collected data from a retrospective study of 4966 patients diagnosed with a FGID (irritable bowel syndrome, dyspepsia, or constipation) and mood or anxiety disorder at general practices in the United Kingdom (health care seekers) over an average period of 13.1 years; we recorded which diagnosis appeared first and compared these with patients' sex and socioeconomic factors. We also collected data from a population study of 1002 randomly selected individuals in Australia (non-heath care seekers) followed from 1997 through 2009; we determined whether subjects were free of either FGID or an anxiety or mood disorder at baseline but developed either one after a 12-year follow-up period. RESULTS: Among the 4966 health care seekers, 3279 patients were diagnosed with a mood or anxiety disorder before an FGID (ratio of 2:1). This ratio increased with socioeconomic disadvantage. The time period between diagnosis of mood or anxiety disorder and FGID was longer (median, 3.5 years) than time period between diagnosis of an FGID and a mood or anxiety disorder (median, 1.8 years). Among non-heath care seekers (population study), equal proportions were diagnosed with a mood or anxiety disorder before versus after an FGID. CONCLUSIONS: In an analysis of data from a study of patients and a population-based study of individuals with these diagnoses, we found 2-fold more patients to receive a diagnosis of a mood or anxiety disorder before an FGID, but equal proportions of individuals in the population to be diagnosed with the mood or anxiety disorder before versus after an FGID. Among patients, the mood or anxiety disorder was on average diagnosed more than 3 years before the FGID, offering opportunity for prevention. Our findings support a role for adverse socioeconomic factors in development of FGIDs in patients with psychological disorders.

Undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI disorder patients with diarrhea or abdominal pain.

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.