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.

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.

Efficacy and safety of STW 5-II for functional dyspepsia treatment: a patient data-based meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a chronic relapsing gastroduodenal disorder with limited treatment options. Herbal products, like the six-herb combination STW5-II, can target multiple FD gastrointestinal symptoms. In this meta-analysis, we evaluated the efficacy and safety of STW 5-II for overall FD, and key symptoms, based on Rome IV criteria. SUMMARY: We systematically screened the literature for randomized controlled clinical studies testing STW 5-II in FD. Meta-analysis was performed using data from individual patients with at least one key FD symptom (fullness, early satiety, or epigastric pain) of at least moderate severity at baseline. ANCOVA-based meta-analyses were performed on improvements in the total symptom sum score, and single symptoms, after 4 and 8 weeks. Safety data were analyzed by calculating odds ratios (ORs) for all adverse events. Four randomized controlled trials, including 613 patients, were identified, and two were eligible for efficacy analysis. STW 5-II significantly improved the FD symptom sum score (mean difference of 1.74 after 4 weeks, and 2.07 after 8 weeks), and key FD symptoms of fullness (0.28 and 0.29), early satiety (0.25 and 0.26), and epigastric/upper abdominal pain (0.26 and 0.3). Treatment-related or severe adverse events did not differ between STW5-II and placebo. KEY MESSAGES: The available data support that in patients meeting Rome IV criteria for FD, STW 5-II significantly improves overall FD and key symptoms after 4 and 8 weeks of treatment, with no safety difference compared to placebo. Thus, STW 5-II can be considered an effective and safe treatment option for FD.

Efficacy and safety of biologics in primary sclerosing cholangitis with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. RESULTS: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics. CONCLUSIONS: Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.

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.

Exome sequencing identifies homozygous variants in MBOAT7 associated with neurodevelopmental disorder.

Intellectual disability (ID) is a large group of neurodevelopmental disorders characterized by a congenital limitation in intellectual functioning (reasoning, learning, and problem solving), adaptive behavior (conceptual, social, and practical skills), originated at birth and manifested before the age of 18. By whole exome sequencing of five consanguineous Pakistani families presenting hallmark features of ID, global developmental delay, aggressive and self-injurious behaviors, microcephaly, febrile seizures and facial dysmorphic features, we identified three novel homozygous missense variants (NM_024298.5: c.588G > T; p.Trp196Cys, c.736 T > C; p.Tyr246His and c.524A > C; p. Asp175Ala) and one rare homozygous in-frame deletion variant (c.758_778del;p.Glu253_Ala259del) in membrane-bound O-acyltransferase family member 7 (MBOAT7) gene previously associated with autosomal recessive neurodevelopmental disorder. The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic MBOAT7 variants in five cases of autosomal recessive ID further highlight the importance of this genes in proper brain function and development.

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia.

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.

Unravelling the controversy with small intestinal bacterial overgrowth.

PURPOSE OF REVIEW: The aim of this review is to summarize the current and emergent approaches to characterize the small intestinal microbiota and discuss the treatment options for management of small intestinal bacterial overgrowth (SIBO). RECENT FINDINGS: This review captures the growing body of evidence for the role of SIBO, a type of small intestinal dysbiosis in the pathophysiology various gastrointestinal and extraintestinal disorders. We have highlighted the drawbacks of the available methods for characterizing the small intestinal microbiota and focus on the new culture-independent techniques to diagnose SIBO. Although recurrence is common, targeted modulation of the gut microbiome as a therapeutic option for management of SIBO is associated with improvement in symptoms and quality of life. SUMMARY: As a first step to precisely characterize the potential link between SIBO and various disorders, we need to address the methodological limitations of the available traditional tests for diagnosing SIBO. There is an urgency to develop culture independent techniques that can be routinely used in clinical setting, that will enable characterization of the gastrointestinal microbiome and explore the response to antimicrobial therapy including the links between long-lasting symptom resolution and the microbiome.

Overlap of disorders of gut-brain interaction: a systematic review and meta-analysis.

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 (I2=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.

Evaluation of small intestinal bacterial overgrowth.

INTRODUCTION: There has been phenomenal interest concerning gut microbiota dysbiosis including small intestinal bacterial overgrowth (SIBO). However, the diagnostic methods for SIBO are still unsatisfactory. AREAS COVERED: The current review covers the different invasive and noninvasive tests to diagnose SIBO, their methodology, interpretation, sensitivity, specificity, and limitations based on the selected articles from literature search using searchterms 'small intestinal bacterial overgrowth' AND 'digestive diseases' OR'diagnosis' OR 'hydrogen breath test' in PubMed in December 2022. The current review will cover some potential methods for diagnosis of SIBO that may be of clinical utility in the future. EXPERT OPINION: SIBO was conventionally defined as a total bacterial count >105 colony forming units (CFU) per mL on quantitative culture of upper gut aspirate. The threshold for the diagnosis of SIBO has been reduced to >103CFU per mL of aspirate recently. Considering the invasiveness of collecting upper gut aspirate, need for laboratory infrastructure and manpower to culture it, noninvasive hydrogen breath tests (HBT) became popular. However, due to the poor sensitivity and specificity of HBT to diagnose SIBO, their utility is being challenged. A new technology of measuring intra-luminal hydrogen gas has a potential to bring a paradigm shift in the diagnostic tests for SIBO.

Small Intestinal Bacterial Overgrowth Complicating Gastrointestinal Manifestations of Systemic Sclerosis: A Systematic Review and Meta-analysis.

Background/Aims: Systemic sclerosis (SSc) often is complicated by small intestinal bacterial overgrowth (SIBO). A systematic review and meta-analysis thus examined the prevalence of SIBO in SSc (SSc-subtypes), identify risk factors for SIBO in SSc and the effects of concomitant SIBO on gastrointestinal symptoms in SSc. Methods: We searched electronic databases until January-2022 for studies providing prevalence rates of SIBO in SSc. The prevalence rates, odds ratio (OR) and 95% confidence intervals (CI) of SIBO in SSc and controls were calculated. Results: The final dataset comprised 28 studies with 1112 SSc-patients and 335 controls. SIBO prevalence in SSc-patients was 39.9% (95% CI, 33.1-47.1; P = 0.006), with considerable heterogeneity, (I2 = 76.00%, P < 0.001). As compared to controls, there was a 10-fold increased SIBO prevalence in SSc-patients (OR, 9.6; 95% CI, 5.6-16.5; P < 0.001). The prevalence of SIBO was not different in limited cutaneous SSc as compared to diffuse cutaneous SSc (OR, 1.01; 95% CI, 0.46-2.20; P = 0.978). Diarrhea (OR, 5.9; 95% CI, 2.9-16.0; P = 0.001) and the association between SIBO in SSc and proton pump inhibitor use (OR, 2.3; 95% CI, 0.8-6.4; P = 0.105) failed statistical significance. Rifaximin was significantly more effective as compared to rotating antibiotic in eradicating SIBO in SSc-patients (77.8% [95% CI, 64.4-87.9]) vs 44.8% [95% CI, 31.7-58.4]; P < 0.05). Conclusions: There is a 10-fold increased prevalence of SIBO in SSc, with similar SIBO prevalence rates in SSc-subtypes. Antimicrobial therapy of SIBO-positive SSc-patients with diarrhea should be considered. However, the results must be interpreted with caution due to substantial unexplained heterogeneity in the prevalence studies, and the low sensitivity and specificity of the diagnostic tests suggesting that the reliability of the evidence may be low.

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.

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.

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.

Laparoscopic fundoplication versus laparoscopic Roux-en-Y gastric bypass for gastro-oesophageal reflux disease in obese patients: protocol for a randomized clinical trial.

BACKGROUND: Laparoscopic fundoplication (LF) is the standard surgical procedure for the treatment of gastro-oesophageal reflux disease (GORD). Laparoscopic Roux-en-Y gastric bypass (LRYGB) is commonly performed to achieve weight loss in obese patients, but it also has anti-reflux properties. Hence, in the obese population suffering from GORD, LRYGB could be an alternative to LF. The aim of this trial will be to compare LF and LRYGB in an obese population presenting with GORD and being considered for surgery. METHODS: This will be an investigator-initiated randomized clinical trial. The research population will be obese patients (BMI 30-34.9 with waist circumference more than 88 cm (women) or more than 102 cm (men), or BMI 35-40 with any waist circumference) referred to a public hospital for consideration of anti-reflux surgery. The primary aim of the study will be to determine the efficacy of LF compared with LRYGB on subjective and objective control of GORD. Secondary aims include determining early and late surgical morbidity and the side-effect profile of LF compared with LRYGB and to quantify any non-reflux benefits of LRYGB (including overall quality of life) compared with LF. CONCLUSION: This trial will determine whether LRYGB is effective and acceptable as an alternative to LF for the surgical treatment of GORD in obese patients Registration number: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000636752p (https://www.anzctr.org.au/).

How frequent are vancomycin-resistant enterococci in patients with primary sclerosing cholangitis and ulcerative colitis treated with oral vancomycin?

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.

Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association.

In the clinical setting, small intestinal bacterial overgrowth (SIBO) is a frequent, but under-diagnosed entity. SIBO is linked to various gastrointestinal (GI) and non-GI disorders with potentially significant morbidity. The optimal management of SIBO is undefined while there is a lack of published consensus guidelines. Against this background, under the auspices of the Indian Neurogastroenterology and Motility Association (INMA), formerly known as the Indian Motility and Functional Diseases Association (IMFDA), experts from the Asian-Pacific region with extensive research and clinical experience in the field of gut dysbiosis including SIBO developed this evidence-based practice guideline for the management of SIBO utilizing a modified Delphi process based upon 37 consensus statements, involving an electronic voting process as well as face-to-face meetings and review of relevant supporting literature. These statements include 6 statements on definition and epidemiology; 11 on etiopathogenesis and pathophysiology; 5 on clinical manifestations, differential diagnosis, and predictors; and 15 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservations was 80% or higher, the statement was regarded as accepted. The members of the consensus team consider that this guideline would be valuable to inform clinical practice, teaching, and research on SIBO in the Asian-Pacific region as well as in other countries.

The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity.

Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function, psychiatric comorbidities, gut-homing immune cells, and duodenal mucosa-associated microbiome (d-MAM) in FGID patients and controls with and without self-reported wheat sensitivity (SR-NCWS). We recruited 40 FGID patients and 20 controls referred by GPs for treatment. Gastrointestinal/extraintestinal symptoms, visceral sensory function, psychological comorbidities, and SR-NCWS were assessed in a standardized approach. Peripheral gut homing T-cells (CD4+α4+ß7+CCR9+/CD8+α4+ß7+CCR9+) were quantified, and the d-MAM was assessed by DNA sequencing for 46 subjects. Factors of bacterial genera were extracted utilizing factor analysis with varimax rotation and factors univariately associated with FGID or SR-NCWS included in a subsequent multivariate analysis of variance to identify statistically independent discriminators. Anxiety scores (p < .05) and increased symptom responses to a nutrient challenge (p < .05) were univariately associated with FGID. Gut homing T-cells were increased in FGID patients with SR-NCWS compared to other groups (p all <0.05). MANOVA revealed that anxiety (p = .03), visceral sensory function (p = 0.007), and a d-MAM factor comprise members of the Alloprevotella, Prevotella, Peptostreptococcus, Leptotrichia, and Veillonella lineages were significantly (p = .001) associated with FGID, while gut homing CD4+α4+ ß7+CCR9+ T-cells were associated (p = .002) with SR-NCWS. Compared to controls, patients with and without SR-NCWS show that there are shifts in the amplicon sequence variants within specific bacterial genera between the FGID subgroups (particularly Prevotella and Streptococcus) as well as distinct bacterial taxa discriminatory for the two different FGID subtypes. Compared to controls, both FGID patients with and without SR-NCWS have an increased symptom response to a standardized nutrient challenge and increased anxiety scores. The FGID patients with SR-NCWS - as compared to FGID without SR-NCWS (and controls without SR-NCWS) - have increased gut homing T-cells. The d-MAM profiles suggest species and strain-based variations between the two FGID subtypes and in comparison to controls.