ORMDL3 regulates NLRP3 inflammasome activation by maintaining ER-mitochondria contacts in human macrophages and dictates ulcerative colitis patient outcome.

Genome-wide association studies in inflammatory bowel disease have identified risk loci in the orosomucoid-like protein 3/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) gene to confer susceptibility to ulcerative colitis (UC), but the underlying functional relevance remains unexplored. Here, we found that a subpopulation of the UC patients who had higher disease activity shows enhanced expression of ORMDL3 compared to the patients with lower disease activity and the non-UC controls. We also found that the patients showing high ORMDL3 mRNA expression have elevated interleukin-1ß cytokine levels indicating positive correlation. Further, knockdown of ORMDL3 in the human monocyte-derived macrophages resulted in significantly reduced interleukin-1ß release. Mechanistically, we report for the first time that ORMDL3 contributes to a mounting inflammatory response via modulating mitochondrial morphology and activation of the NLRP3 inflammasome. Specifically, we observed an increased fragmentation of mitochondria and enhanced contacts with the endoplasmic reticulum (ER) during ORMDL3 over-expression, enabling efficient NLRP3 inflammasome activation. We show that ORMDL3 that was previously known to be localized in the ER also becomes localized to mitochondria-associated membranes and mitochondria during inflammatory conditions. Additionally, ORMDL3 interacts with mitochondrial dynamic regulating protein Fis-1 present in the mitochondria-associated membrane. Accordingly, knockdown of ORMDL3 in a dextran sodium sulfate -induced colitis mouse model showed reduced colitis severity. Taken together, we have uncovered a functional role for ORMDL3 in mounting inflammation during UC pathogenesis by modulating ER-mitochondrial contact and dynamics.

FODMAP meal challenge test: a novel investigation to predict response to low-FODMAP diet in non-constipating irritable bowel syndrome.

BACKGROUND: Though a low-FODMAP diet improves 50% irritable bowel syndrome (IBS) patients, regional dietary variations, vegetarianism, and long-term nutritional consequences challenge its implementation. We aimed developing a FODMAP meal challenge test (FMCT). We prospectively studied whether (i) high- than low-FODMAP foods produce more breath H2 among IBS patients than controls; (ii) post-meal symptoms relate to breath H2 ; and (iii) novel FMCT predicts response to a low-FODMAP diet? METHODS: Forty Rome III IBS and 20 healthy controls underwent an eight-hour H2 breath test following a low- (rice, brinjal, corn, and banana [450 Kcal]) and a high-FODMAP meal (wheat, kidney bean, pulse, and card [450 Kcal]). Breath H2 (every 15 min) and symptoms following low- and high-FODMAP meals were recorded. IBS-symptom severity scores were recorded every month for 3-months on low-FODMAP diet. RESULTS: Forty Rome III IBS (19 Rome IV positive) were comparable to 20 controls in age and gender. IBS patients (n = 39 excluding one H2 non-producer) and controls produced more breath H2 after high- (greater in IBS) than low-FODMAP meal. Post-meal symptoms were commoner in IBS (4/40 [10%] and 27/40 [67.5%] with low- and high-FODMAP, respectively [P < 0.00001]; none in healthy). IBS patients developing post-high-FODMAP meal symptoms produced greater H2 (18 PPM [IQR 10.5-23] vs 6 [0-7.2]; P < 0.001). A positive FMCT (breath H2  > 10 PPM above basal with symptoms following high-FODMAP food) had sensitivity, specificity, and diagnostic accuracy of 78.6%, 66.6%, and 75.6%, respectively, to predict low-FODMAP diet response. CONCLUSIONS: The novel FMCT predicts response to a low-FODMAP diet in IBS.

Gastrointestinal involvement in post-acute Coronavirus disease (COVID)-19 syndrome.

PURPOSE OF REVIEW: Ten percentage of patients with coronavirus disease (COVID)-19 report having gastrointestinal (GI) symptoms as severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) not only infects the pulmonary but also the GI tract. GI infections including that due to viral infection is known to cause postinfection disorders of gut-brain interaction (DGBI); hence, we wish to review the long-term GI consequences following COVID-19, particularly post-COVID-19 DGBI. RECENT FINDINGS: At least 12 cohort studies, four of which also included controls documented the occurrence of post-COVID-19 DGBI, particularly IBS following COVID-19. The risk factors for post-COVID-19 DGBI included female gender, symptomatic COVID-19, particularly GI symptoms, the severity of COVID-19, the occurrence of anosmia and ageusia, use of antibiotics and hospitalization during the acute illness, persistent GI symptoms beyond 1 month after recovery, presence of mental health factors, The putative mechanisms for post-COVID-19 DGBI include altered gut motility, visceral hypersensitivity, gut microbiota dysbiosis, GI inflammation, and immune activation, changes in intestinal permeability, and alterations in the enteroendocrine system and serotonin metabolism. SUMMARY: Long-term sequelae of SARS-CoV2 infection may persist even after recovery from COVID-19. Patients with COVID-19 are more likely to develop post-COVID-19 IBS than healthy controls. Post-COVID-19 IBS may pose a substantial healthcare burden to society.

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.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: A case-control study.

BACKGROUND AND AIM: Because acute infectious gastroenteritis may cause post-infection irritable bowel syndrome and functional dyspepsia and the severe acute respiratory syndrome coronavirus-2 affects gastrointestinal (GI) tract, coronavirus disease-19 (COVID-19) may cause post-infection-functional GI disorders (FGIDs). We prospectively studied the frequency and spectrum of post-infection-FGIDs among COVID-19 and historical healthy controls and the risk factors for its development. METHODS: Two hundred eighty patients with COVID-19 and 264 historical healthy controls were followed up at 1 and 3 months using translated validated Rome Questionnaires for the development of chronic bowel dysfunction (CBD), dyspeptic symptoms, and their overlap and at 6-month for IBS, uninvestigated dyspepsia (UD) and their overlap. Psychological comorbidity was studied using Rome III Psychosocial Alarm Questionnaire. RESULTS: At 1 and 3 months, 16 (5.7%), 16 (5.7%), 11 (3.9%), and 24 (8.6%), 6 (2.1%), 9 (3.2%) of COVID-19 patients developed CBD, dyspeptic symptoms, and their overlap, respectively; among healthy controls, none developed dyspeptic symptoms and one developed CBD at 3 months (P < 0.05). At 6 months, 15 (5.3%), 6 (2.1%), and 5 (1.8%) of the 280 COVID-19 patients developed IBS, UD, and IBS-UD overlap, respectively, and one healthy control developed IBS at 6 months (P < 0.05 for all except IBS-UD overlap). The risk factors for post-COVID-19 FGIDs at 6 months included symptoms (particularly GI), anosmia, ageusia, and presence of CBD, dyspeptic symptoms, or their overlap at 1 and 3 months and the psychological comorbidity. CONCLUSIONS: This is the first study showing COVID-19 led to post-COVID-19 FGIDs. Post-COVID-19 FGIDs may pose a significant economic, social, and healthcare burden to the world.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Impact of the coronavirus disease 2019 pandemic on irritable bowel syndrome.

BACKGROUND AND AIM: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. METHODS: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. RESULTS: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. CONCLUSION: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome.

BACKGROUND & AIMS: The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience. METHODS: The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members. RESULTS: PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms. CONCLUSIONS: Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.

Marshall and Warren Lecture 2019: A paradigm shift in pathophysiological basis of irritable bowel syndrome and its implication on treatment.

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder (FGID), has often been considered rather inappropriately as psychogenic in the past. Though psychological issues are important comorbidities in a proportion of IBS patients, the evidences are far from enough to label this condition as psychogenic only. In the recent past, evidences are emerging that underscores the concept supporting pure psychogenic theory of IBS and suggest this disorder to be rather microorganic. Accordingly, a move of Rome IV Committee attempting to delete the term "functional" and designating these to be disorders of "gut-brain interaction" rather than that of "brain-gut interaction," it emphasizes the importance of the gut over the brain in the pathogenesis. The introduction of the concept of multidimensional clinical profile in Rome IV requires attention to diagnostic category of FGID, overlap, severity, psychological issues, and physiological dysfunction or biomarkers; this attempts to recognize clinical variability and multidimensionality of pathophysiology and management of these disorders. The recognition of the biological factors in the pathogenesis of IBS is a significant paradigm shift in the recent time. This is somewhat similar to the progress in the pathogenesis of peptic ulcer disease from psychological factor to acid to Helicobacter pylori infection. It is expected that in the near future, therapeutic modalities targeting the different pathogenic mechanisms of different subtypes of IBS may bring revolution in management of the disorder.

A meta-analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome.

BACKGROUND: Enteric microbiota is increasingly being recognized as an important factor in the pathogenesis of irritable bowel syndrome (IBS). The reported prevalence of small intestinal bacterial overgrowth (SIBO) in subjects with IBS is highly variable, and there is no consensus on the role of SIBO in different subtypes of IBS, and indications and methods of testing. METHODS: A comprehensive literature search was performed for studies applying tests for SIBO in subjects with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of SIBO in subjects with IBS using different tests. The odds ratios of SIBO among subjects with IBS as compared with healthy controls using different tests were calculated. RESULTS: Of the available studies (22, 17, 5, and 3 using lactulose and glucose hydrogen breath tests [LHBT and GHBT], jejunal aspirate culture, and more than one tests, respectively) meeting the inclusion criteria, 36.7% (95% confidence interval [CI] 24.2-44.6) had a positive test for SIBO. Patients with IBS were 2.6 (95% CI 1.3-6.9) and 8.3 (95% CI 3.0-5.9) times more likely to have a positive test for SIBO as compared with healthy controls using GHBT and jejunal aspirate culture, respectively. Patients with diarrhea-predominant IBS were more likely to have positive GHBT as compared with the other subtypes. CONCLUSIONS: Patients with IBS were more likely to have SIBO as compared with healthy subjects using GHBT and jejunal aspirate culture but not using LHBT. Patients with diarrhea-predominant IBS more often have SIBO.

"It ain't over till it's over!" Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic.

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health-care needs of COVID-19 patients. During the adaptation phase, GI services are calibrated towards a "new normal," and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long-term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence-based decision-making during the adaptation and consolidation phases.

Rome Foundation-Asian working team report: Asian functional gastrointestinal disorder symptom clusters.

OBJECTIVE: Functional gastrointestinal disorders (FGIDs) are diagnosed by the presence of a characteristic set of symptoms. However, the current criteria-based diagnostic approach is to some extent subjective and largely derived from observations in English-speaking Western patients. We aimed to identify latent symptom clusters in Asian patients with FGID. DESIGN: 1805 consecutive unselected patients with FGID who presented for primary or secondary care to 11 centres across Asia completed a cultural and linguistic adaptation of the Rome III Diagnostic Questionnaire that was translated to the local languages. Principal components factor analysis with varimax rotation was used to identify symptom clusters. RESULTS: Nine symptom clusters were identified, consisting of two oesophageal factors (F6: globus, odynophagia and dysphagia; F9: chest pain and heartburn), two gastroduodenal factors (F5: bloating, fullness, belching and flatulence; F8 regurgitation, nausea and vomiting), three bowel factors (F2: abdominal pain and diarrhoea; F3: meal-related bowel symptoms; F7: upper abdominal pain and constipation) and two anorectal factors (F1: anorectal pain and constipation; F4: diarrhoea, urgency and incontinence). CONCLUSION: We found that the broad categorisation used both in clinical practice and in the Rome system, that is, broad anatomical divisions, and certain diagnoses with long historical records, that is, IBS with diarrhoea, and chronic constipation, are still valid in our Asian societies. In addition, we found a bowel symptom cluster with meal trigger and a gas cluster that suggests a different emphasis in our populations. Future studies to compare a non-Asian cohort and to match to putative pathophysiology will help to verify our findings.

The role of the microbiome and the use of probiotics in gastrointestinal disorders in adults in the Asia-Pacific region - background and recommendations of a regional consensus meeting.

The Asia-Pacific region is diverse, with regard to ethnicity, culture, and economic development incorporating some of the world's least and most developed nations. Gastrointestinal diseases are common in the Asia-Pacific region, and their prevalence, presentation, and management vary considerably within the region. There is growing evidence for an important role for the human gut microbiota in gastrointestinal health. As a consequence, geographic variations in the composition of the gut microbiota may contribute to variations in both the prevalence and response to therapy of specific diseases. Probiotics have been proposed as a valuable option in the prevention and treatment of a number of gastrointestinal illnesses, but the quality of available evidence to support their efficacy is variable. A meeting of international experts in adult and pediatric gastroenterology was held at the Sorbonne University, Paris, France, on April 11 and 12, 2016, to discuss current evidence supporting the use of probiotics in gastrointestinal disorders in the Asia-Pacific region. This article provides an overview of the discussions held at this meeting and recommends the formation of an Asia-Pacific Consortium on Gut Microbiota similar to those established in Europe and North America.

Management of achalasia cardia: Expert consensus statements.

Achalasia cardia (AC) is a frequently encountered motility disorder of the esophagus resulting from an irreversible degeneration of neurons. Treatment modalities are palliative in nature, and there is no curative treatment available for AC as of now. Significant advancements have been made in the management of AC over last decade. The introduction of high resolution manometry and per-oral endoscopic myotomy (POEM) has strengthened the diagnostic and therapeutic armamentarium of AC. High resolution manometry allows for the characterization of the type of achalasia, which in turn has important therapeutic implications. The endoscopic management of AC has been reinforced with the introduction of POEM that has been found to be highly effective and safe in palliating the symptoms in short-term to mid-term follow-up studies. POEM is less invasive than Heller's myotomy and provides the endoscopist with the opportunity of adjusting the length and orientation of esophageal myotomy according to the type of AC. The management of achalasia needs to be tailored for each patient, and the role of pneumatic balloon dilatation, POEM, or Heller's myotomy needs to be revisited. In this review, we discuss the important aspects of diagnosis as well as management of AC. The statements presented in the manuscript reflect the cumulative efforts of an expert consensus group.