Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

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 Histological Gastritis in a Community Population and Association with Epigastric Pain.

BACKGROUND AND AIMS: Gastritis is a common histological diagnosis, although the prevalence is decreasing in developed populations, alongside decreasing prevalence of H. pylori infection. We sought to determine the prevalence of the etiology of gastritis in a Swedish population sample and to analyze any associations with symptoms, an area of clinical uncertainty. METHODS: Longitudinal population-based study based in Östhammar, Sweden. A randomly sampled adult population completed a validated gastrointestinal symptom questionnaire (Abdominal Symptom Questionnaire, ASQ) in 2011 (N = 1175). Participants < 80 years of age and who were eligible were invited to undergo esophagogastroduodenoscopy (EGD) (N = 947); 402 accepted and 368 underwent EGD with antral and body biopsies (average 54.1 years, range 20-79 years; 47.8% male) with H. pylori serology. RESULTS: Gastritis was found in 40.2% (148/368; 95% CI 35.2-45.2%). By rank, the most common histological subtype was reactive (68/148; 45.9%), then H. pylori (44/148; 29.7%), chronic non-H. pylori (29/148; 19.6%), and autoimmune (4/148; 2.7%). Gastritis was significantly associated with older age and H. pylori status (p < 0.01). Gastritis subjects were divided into three histological categories: chronic inactive inflammation, autoimmune gastritis, and active inflammation; there was no difference in the presence of upper gastrointestinal symptoms when categories were compared to cases with no pathological changes. Functional dyspepsia or gastroesophageal reflux were reported in 25.7% (38/148) of those with gastritis (any type or location) versus 34.1% (75/220) with no pathological changes (p = 0.32). Epigastric pain was more common in chronic H. pylori negative gastritis in the gastric body (OR = 3.22, 95% CI 1.08-9.62). CONCLUSION: Gastritis is common in the population with a prevalence of 40% and is usually asymptomatic. Chronic body gastritis may be associated with epigastric pain, but independent validation is required to confirm these findings. Clinicians should not generally ascribe symptoms to histological gastritis.

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.

Pregnancy period and early-life risk factors for inflammatory bowel disease: a Northern Finland birth cohort 1966 study.

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher's exact test and logistic regression. RESULTS: In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn's disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70-17.3). Breastfeeding (OR = 0.18, 95% CI 0.08-0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21-0.89) were negatively associated with CD. CONCLUSIONS: Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

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.

Factors Associated With Placebo Treatment Response in Functional Dyspepsia Clinical Trials.

INTRODUCTION: Controlling for potential placebo effects is an important aspect of gaining an accurate estimate of how much the therapy alone changes patient symptoms or other end points. When the placebo effect is large, this can lead to only a small fraction of changes seen in the active therapy group being attributed to the therapy itself. This problem has been well studied in some disorders of brain-gut interaction but not in functional dyspepsia where placebo response rates of 40% and higher have been reported. Understanding risk factors for placebo response might lead to changes in trial design that could reduce the magnitude of the problem. This study sought to identify risk factors for the placebo effect in a functional dyspepsia clinical trial with a longer-term aim of suggesting trial design changes that might minimize the problem. METHODS: A secondary analysis of the clinical trial data was undertaken using 2 arms deemed to involve placebo therapy. Potential predictors were drawn from a wide range of patient characteristics including psychological, clinical, and physiological features. RESULTS: Predictors of a stronger placebo effect on the gastrointestinal symptom rating scale included higher functional dyspepsia symptom burden at baseline ( b = -0.101), coexisting irritable bowel syndrome ( b = -0.436), and higher scores on the Nepean Dyspepsia Index eat/drink domain (-0.005). Baseline symptom burden and coexisting irritable bowel syndrome were found to be independent placebo predictors, explaining 13% of the variance in change in gastrointestinal symptom rating scale. Anxiety, childhood sexual abuse, sleep amount, and frequent abdominal pain were also found to be predictors of change in individual symptom scores. DISCUSSION: The findings of this study yield actionable insights into trial methodology that may help to reduce the magnitude of the placebo effect in future functional dyspepsia treatment trials.

Association Between Anxiety/Depression and Gastroesophageal Reflux: A Systematic Review and Meta-Analysis.

INTRODUCTION: An association between gastroesophageal reflux disease (GERD) and common psychiatric conditions, most notably anxiety and depression, has been reported. However, the magnitude of this association is poorly understood. Therefore, we aimed to systematically assess this issue. METHODS: We comprehensively searched multiple bibliographic databases (Embase, PubMed, Scopus, and Web of Science) from inception to May 15, 2023. We retrieved observational studies that reported the prevalence of anxiety and/or depressive symptoms diagnosed by validated questionnaires in ≥100 adults (aged 18 years or older) with GERD. We also included cohort studies that explored the risk of incident GERD in subjects with anxiety/depression vice versa scenario. Finally, we included Mendelian randomization studies that assessed the cause-and-effect relationship between anxiety/depression and GERD. The extracted data were combined using a random-effects model. RESULTS: In total, 36 eligible studies were included. The pooled prevalences of anxiety and depressive symptoms were 34.4% (95% confidence interval [CI] 24.7-44.2; I2 = 99.4%) and 24.2% (95% CI 19.9-28.5; I2 = 98.8%) in subjects with GERD based on 30 studies, respectively. Both anxiety and depressive symptoms were more common in subjects with GERD compared with those in healthy controls (odds ratio = 4.46 [95% CI 1.94-10.25] and odds ratio = 2.56 [95% CI 1.11-5.87], respectively). According to 3 cohort studies, subjects with GERD were at an increased risk of developing anxiety/depression and vice versa. Finally, 3 Mendelian randomization studies showed that genetic liability to these mood disorders is linked to an increased risk of developing GERD and vice versa. DISCUSSION: Up to 1 in 3 subjects with GERD experience anxiety and depression. There is likely a bidirectional causal relationship between anxiety/depression and GERD.

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.

Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis: a population-based colonoscopy study.

BACKGROUND: The etiopathogenesis of diverticular disease is unknown. OBJECTIVE: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study. METHODS: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not. RESULTS: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027). CONCLUSIONS: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.

Does the microbiome play a role in the pathogenesis of colonic diverticular disease? A systematic review.

BACKGROUND AND AIMS: The role of the microbiota in diverticulosis and diverticular disease is underexplored. This systematic review aimed to assess all literature pertaining to the microbiota and metabolome associations in asymptomatic diverticulosis, symptomatic uncomplicated diverticular disease (SUDD), and diverticulitis pathophysiology. METHODS: Seven databases were searched for relevant studies published up to September 28, 2022. Data were screened in Covidence and extracted to Excel. Critical appraisal was undertaken using the Newcastle Ottawa Scale for case/control studies. RESULTS: Of the 413 papers screened by title and abstract, 48 full-text papers were reviewed in detail with 12 studies meeting the inclusion criteria. Overall, alpha and beta diversity were unchanged in diverticulosis; however, significant changes in alpha diversity were evident in diverticulitis. A similar Bacteroidetes to Firmicutes ratio compared with controls was reported across studies. The genus-level comparisons showed no relationship with diverticular disease. Butyrate-producing microbial species were decreased in abundance, suggesting a possible contribution to the pathogenesis of diverticular disease. Comamonas species was significantly increased in asymptomatic diverticulosis patients who later developed diverticulitis. Metabolome analysis reported significant differences in diverticulosis and SUDD, with upregulated uracil being the most consistent outcome in both. No significant differences were reported in the mycobiome. CONCLUSION: Overall, there is no convincing evidence of microbial dysbiosis in colonic diverticula to suggest that the microbiota contributes to the pathogenesis of asymptomatic diverticulosis, SUDD, or diverticular disease. Future research investigating microbiota involvement in colonic diverticula should consider an investigation of mucosa-associated microbial changes within the colonic diverticulum itself.

Increased mucosal eosinophils in colonic diverticulosis and diverticular disease.

AIMS: Eosinophils contribute to tissue homeostasis, damage, and repair. The mucosa of colonic diverticula has not been evaluated for eosinophils by quantitative histology. We aimed to investigate whether mucosal eosinophils and other immune cells are increased in colonic diverticula. METHODS: Hematoxylin and eosin stained sections from colonic surgical resections (n = 82) containing diverticula were examined. Eosinophils, neutrophils, and lymphocytes, in five high power fields in the lamina propria were counted at the base, neck, and ostia of the diverticulum and counts compared to non-diverticula mucosa. The cohort was further subgrouped by elective and emergency surgical indications. RESULTS: Following an initial review of 10 surgical resections from patients with diverticulosis, a total of 82 patients with colonic resections containing diverticula from the descending colon were evaluated (median age 71.5, 42 M/40F). Eosinophil counts for the entire cohort were increased in the base and neck (median 99 and 42, both P = <0.001) compared with the control location (median 16). Eosinophil counts remained significantly increased in the diverticula base (both P = <0.001) and neck (P = 0.01 and <0.001, respectively) in both elective and emergency cases. Lymphocytes were also significantly increased at the diverticula base compared to controls in both elective and emergency subgroups. CONCLUSION: Eosinophils are significantly and most strikingly increased within the diverticulum in resected colonic diverticula. While these observations are novel, the role of eosinophil and chronic inflammation is as yet unclear in the pathophysiology of colonic diverticulosis and diverticular disease.

Weight loss with subcutaneous semaglutide versus other glucagon-like peptide 1 receptor agonists in type 2 diabetes: a systematic review.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce elevated blood glucose levels and induce weight loss. Multiple GLP-1 RAs and one combined GLP-1/glucose-dependent insulinotropic polypeptide agonist are currently available. This review was conducted with the aim of summarising direct comparisons between subcutaneous semaglutide and other GLP-1 RAs in individuals with type 2 diabetes (T2D), particularly with respect to efficacy for inducing weight loss and improving other markers of metabolic health. This systematic review of PubMed and Embase from inception to early 2022 was registered on PROSPERO and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Of the 740 records identified in the search, five studies fulfilled the inclusion criteria. Comparators included liraglutide, exenatide, dulaglutide and tirzepatide. In the identified studies, multiple dosing regimens were utilised for semaglutide. Randomised trials support the superior efficacy of semaglutide over other GLP-1 RAs with respect to weight loss in T2D, but tirzepatide is more effective than semaglutide.

In active Crohn disease, risankizumab increased clinical remission and endoscopic response at 12 wk.

SOURCE CITATION: D'Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399:2015-30. 35644154.

In drug-refractory IBS, group CBT with interoceptive exposure improved symptoms and QoL at 13 wk.

SOURCE CITATION: Kikuchi S, Oe Y, Ito Y, et al. Group cognitive-behavioral therapy with interoceptive exposure for drug-refractory irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2022;117:668-77. 35103022.

Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field.

The US Food and Drug Administration hosted a workshop on July 21, 2021, to discuss the disease characteristics, natural history, and end points to assess treatment benefit in patients with eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE). Notably, EGIDs beyond EoE, such as eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis, herein referred to as non-EoE EGIDs, are understudied relative to EoE. This workshop provided a forum for open discussion among stakeholders-medical professionals (including their societies and research groups), Food and Drug Administration representatives, an industry representative, and a patient representative-to facilitate drug development. Experts in many disciplines related to EGIDs, including allergy, immunology, epidemiology, gastroenterology, and pathology, and both adult and pediatric clinicians contributed. Herein, we discuss some of the insights of the material presented at the meeting and present perspectives on moving the field forward toward drug approval.

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.

Long-Term Outcome of Multidisciplinary Versus Standard Gastroenterologist Care for Functional Gastrointestinal Disorders: A Randomized Trial.

BACKGROUND & AIMS: Functional gastrointestinal disorders are common and costly to the healthcare system. In the Multidisciplinary Treatment of Functional Gastrointestinal Disorders study, we demonstrated that multidisciplinary care resulted in superior clinical and cost outcomes, when compared with standard gastroenterologist-only care at end of treatment. In this study we evaluate the longer-term outcomes. METHODS: In a single-center, pragmatic trial patients with Rome IV criteria-defined functional gastrointestinal disorders were randomized 1:2 to a gastroenterologist-only standard care vs a multidisciplinary clinic comprising gastroenterologists, dietitians, gut hypnotherapists, psychiatrists, and biofeedback physiotherapists. Outcomes in this study were assessed 12 months after the end of treatment. Global symptom improvement was assessed by using a 5-point Likert scale. Symptoms, specific disorder status, psychological state, quality of life, and cost were additional outcomes. A modified intention-to-treat analysis was performed. RESULTS: Of 188 randomized patients, 143 (46 standard care, 97 multidisciplinary) formed the longer-term modified intention-to-treat analysis. Sixty-two percent of multidisciplinary clinic patients saw allied clinicians. Sixty-five percent (30/46) standard care versus 76% (74/97) multidisciplinary clinic patients achieved global symptom improvement 12 months after end of treatment (P = .17), whereas 20% (9/46) versus 37% (36/97) rated their symptoms as "5/5 much better" (P = .04). A ≥50-point reduction in Irritable Bowel Syndrome Severity Scoring System occurred in 38% versus 66% (P = .02), respectively, for irritable bowel syndrome patients. Anxiety and depression were greater in the standard care than multidisciplinary clinic (12 vs 10, P = .19), and quality of life was lower in standard care than the multidisciplinary clinic (0.75 vs 0.77, P =·.03). An incremental cost-effectivness ratio found that for every additional 3555AUD spent in the multidisciplinary clinic, a further quality-adjusted life year was gained. CONCLUSIONS: Twelve months after the completion of treatment, integrated multidisciplinary clinical care achieved a greater proportion of patients with improvement of symptoms, psychological state, quality of life, and cost, compared with gastroenterologist-only care. CLINICAL TRIALS: gov: number NCT03078634.

Evidence-Based and Emerging Diet Recommendations for Small Bowel Disorders.

Diet plays a key role in the manifestation and severity of gastrointestinal symptoms, with increasing research interest on the role of diet in small bowel disorders. There are predominantly 3 small bowel conditions that have potential dietary interventions. Self-reported nonceliac gluten/wheat sensitivity is prevalent. Although gluten is believed to be a potential trigger for symptoms, other components of wheat may also be triggers, including fructans, alpha-amylase trypsin inhibitors, and wheat germ agglutinins. The diagnosis can be challenging, given the lack of validated biomarkers. A gluten-free diet that excludes the abovementioned triggers is the cornerstone of treatment; however, unlike celiac disease, there is uncertainty about the level of adherence or whether the gluten-free diet is a lifelong intervention. Several primary gastrointestinal disorders are associated with an increase in inflammatory cells including eosinophils. Diet seems to be an important driver of disease pathogenesis in eosinophilic gastroenteritis, with elimination and elemental diets showing promise in management, with further robust trials required. Small intestinal bacterial overgrowth is an example of microbial dysbiosis, with renewed interest in diet being postulated to cause an adaptive change of the microbes colonizing the small intestine. However, the diagnosis of small intestinal bacterial overgrowth is limited by a lack of sensitive and specific tests, with significant knowledge gaps in relation to therapeutic measures to manage and cure small intestinal bacterial overgrowth. Currently, antimicrobials are the established management option. There have been significant clinical advances in dietary interventions related to the small bowel, but this area is currently a novel and advancing field for both patients and clinicians.

Immune responses in the irritable bowel syndromes: time to consider the small intestine.

BACKGROUND: Irritable bowel syndrome (IBS) is considered a disorder of gut-brain interaction (DGBI), presenting as chronic abdominal pain and altered defaecation. Symptoms are often food related. Much work in the field has focused on identifying physiological, immune and microbial abnormalities in the colon of patients; however, evidence of small intestinal immune activation and microbial imbalance has been reported in small studies. The significance of such findings has been largely underappreciated despite a growing body of work implicating small intestinal homeostatic imbalance in the pathogenesis of DGBIs. MAIN TEXT: Small intestinal mechanosensation is a characteristic feature of IBS. Furthermore, altered small intestinal barrier functions have been demonstrated in IBS patients with the diarrhoea-predominant subtype. Small intestinal bacterial overgrowth and increased populations of small intestinal mast cells are frequently associated with IBS, implicating microbial imbalance and low-grade inflammation in the pathogenesis of IBS. Furthermore, reports of localised food hypersensitivity responses in IBS patients implicate the small intestine as the site of immune-microbial-food interactions. CONCLUSIONS: Given the association of IBS symptoms with food intake in a large proportion of patients and the emerging evidence of immune activation in these patients, the current literature suggests the pathogenesis of IBS is not limited to the colon but rather may involve dysfunction of the entire intestinal tract. It remains unclear if regional variation in IBS pathology explains the various symptom phenotypes and further work should consider the intestinal tract as a whole to answer this question.