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Perceptions, Definitions, and Therapeutic Interventions for Occasional Constipation: A Rome Working Group Consensus Document.
Brenner, DM, Corsetti, M, Drossman, D, Tack, J, Wald, A
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;(2):397-412
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Abstract
BACKGROUND & AIMS Functional constipation is the most common of the disorders of gut-brain interaction, affecting approximately 12% of the world population. Although classically considered a chronic condition, many individuals experience shorter yet repetitive bouts of constipation representing a different clinical entity. There has been increased interest in this latter disorder, which has recently been classified as occasional constipation. This Rome Foundation working group document reflects the consensus of an international team of specialists who summarized currently available research to provide a working definition of and treatment algorithm for occasional constipation. The recommendations herein are based on current evidence, accounting for gaps in the literature as well as international variance in definitions and health seeking behaviors for constipation. METHODS The committee members reviewed the scientific literature, focusing specifically on occasional constipation, with the understanding that as a new entity, a paucity of data would be available. We used Rome IV research and clinical definitions to establish the framework for our definition of occasional constipation. Where possible, treatment recommendations were determined on the basis of the earliest extractable data from functional constipation studies, focusing on positive results within the first 2 weeks of treatment. We used the Delphi method to create consensus with 100% agreement between the authors. RESULTS An evidence-based review of the literature resulted in the definition of occasional constipation as follows: "individuals who experience the presence of at least 1 functional constipation symptom, in the absence of alarm signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management." Medical management whether seeking medical care or self-treatment was left to the individual's discretion, and we did not include time anchors because these thresholds require further investigation. Polyethylene glycol and stimulant laxatives are recommended as first-line interventions, whereas magnesium-containing compounds are suggested in individuals failing to respond to these therapies. There are insufficient data to make recommendations for using fiber or stool softeners. Prescription laxatives should be reserved for individuals with chronic constipation. CONCLUSIONS Occasional constipation is a unique clinical entity characterized by infrequent but recurrent symptoms. Data are limited because consensus definitions have been lacking. Establishing a standardized definition and therapeutic recommendations provides a framework for future studies focusing on epidemiologic and symptoms-based outcomes. Further studies are needed to confirm and refine these recommendations.
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Nutrition and Disorders of Gut-Brain Interaction.
Scarpellini, E, Balsiger, LM, Broeders, B, Houte, KVD, Routhiaux, K, Raymenants, K, Carbone, F, Tack, J
Nutrients. 2024;(1)
Abstract
BACKGROUND Disorders of gut-brain interaction (DGBIs) have a complex pathophysiology that is often characterized by a relationship between food ingestion and triggering of symptoms. Understanding of the underlying mechanisms and the role of nutrients as a therapeutic target are rapidly evolving. AIMS AND METHODS We performed a narrative review of the literature using the following keywords, their acronyms, and their associations: nutrients, disorders of gut-brain interaction; functional dyspepsia; malabsorption; irritable bowel syndrome; diarrhea; constipation. RESULTS Functional dyspepsia displayed a significant correlation between volume, fat and/or wheat abundance, chemical composition of ingested food and symptoms of early satiety, fullness and weight loss. Carbohydrate malabsorption is related to enzyme deficiency throughout the GI tract. Food composition and richness in soluble vs. non-soluble fibers is related to constipation and diarrhea. The elimination of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) has a significant and non-unidirectional impact on irritable bowel syndrome (IBS) symptoms. CONCLUSIONS Food volume, nutritive and chemical composition, and its malabsorption are associated with symptom generation in DGBIs. Further multicenter, randomized-controlled clinical trials are needed to clarify the underlying pathophysiology.
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Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome.
Van den Houte, K, Colomier, E, Routhiaux, K, Mariën, Z, Schol, J, Van den Bergh, J, Vanderstappen, J, Pauwels, N, Joos, A, Arts, J, et al
Gastroenterology. 2024
Abstract
BACKGROUND AND AIMS The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities. METHODS Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities. RESULTS In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose. CONCLUSION We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.
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Understanding and managing patients with overlapping disorders of gut-brain interaction.
Balsiger, LM, Carbone, F, Raymenants, K, Scarpellini, E, Tack, J
The lancet. Gastroenterology & hepatology. 2023;(4):383-390
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Abstract
Disorders of gut-brain interaction (DGBI) are frequently encountered in clinical practice, and recommendations for diagnosis and management are well established. In a large subset of patients, more than one DGBI diagnosis is present. This group of patients with more than one DGBI diagnosis have higher symptom severity and impact than patients with only one DGBI diagnosis, and the management approach is not well established for those with overlapping diagnoses. This Review aims to guide clinicians to understand, recognise, and manage overlapping DGBI by identifying causes and pitfalls of overlap conditions, and presenting potential practical approaches to diagnosis, treatment, and follow-up. Several clinical factors can contribute to finding overlapping DGBI, including the anatomical basis of the Rome diagnostic criteria, the potential confusion of symptom descriptors, and patients' biases towards higher symptom intensity ratings. Overlapping DGBI could also be caused by mechanistic factors such as pathophysiological mechanisms involving multiple gastrointestinal segments, and the effect of disorders in one segment on sensorimotor function in remote gastrointestinal parts, through neural or hormonal signalling. Key initial steps in the management of overlapping DGBI are detailed history taking, which can be facilitated using pictograms; carefully assessing the relative timing and cohesion of different symptoms; and recognising associated psychosocial dysfunction. Unnecessary technical investigations and complex combination treatment schedules should be avoided. Based on the identification of the dominant symptom pattern and putative underlying pathophysiological mechanisms, a single treatment modality should preferably be initiated, considering the efficacy spectrum of different therapies. Follow-up of the patient's condition allows the therapeutic approach to be adjusted as needed, while avoiding unnecessary additional technical investigations.
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Mechanisms underlying food-related symptoms in disorders of gut-brain interaction: Course ahead in research and clinical practice.
Colomier, E, Algera, JP, Van den Houte, K, Simrén, M, Tack, J
Best practice & research. Clinical gastroenterology. 2023;:101824
Abstract
A subgroup of patients with a disorder of gut-brain interaction (DGBI) report symptoms such as abdominal pain, gas-related symptoms, dyspeptic symptoms and loose stool or urgency after meal intake. Therefore, the effect of several dietary therapies including fibre-rich or restrictive diets have already been studied in patients with irritable bowel syndrome, functional abdominal bloating or distention, and functional dyspepsia. However, there is a paucity of studies in the literature on the mechanisms underlying food-related symptoms. Therefore, this review focuses on these potential mechanisms and explains the role of nutrient sensing and tasting, physical considerations, malabsorption or allergy-like reaction to food and its interaction with microbiota. In addition, it emphasizes the importance of future research and clinical practice regarding food-related symptoms in patients with a DGBI.
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Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis.
Bosman, M, Smeets, F, Elsenbruch, S, Tack, J, Simrén, M, Talley, N, Winkens, B, Masclee, A, Keszthelyi, D
Neurogastroenterology and motility. 2023;(2):e14474
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BACKGROUND Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. METHODS We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. KEY RESULTS We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. CONCLUSIONS AND INFERENCES The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
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Human Genes Involved in the Interaction between Host and Gut Microbiome: Regulation and Pathogenic Mechanisms.
Boccuto, L, Tack, J, Ianiro, G, Abenavoli, L, Scarpellini, E
Genes. 2023;(4)
Abstract
INTRODUCTION The umbrella term "human gut microbiota" describes the complex ecosystem harboring our gut. It includes bacteria, viruses, protozoa, archaea, fungi, and yeasts. This taxonomic classification does not describe its functions, which encompass nutrients digestion and absorption, immune system regulation, and host metabolism. "Gut microbiome" indicates instead the genome belonging to these "microbes" actively involved in these functions. However, the interaction between the host genome and the microbial ones determines the fine functioning of our organism. METHODS We reviewed the data available in the scientific literature on the definition of gut microbiota, gut microbiome, and the data on human genes involved in the interaction with the latter. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, gut microbiome, human genes, immune function, and metabolism. RESULTS Candidate human genes encoding enzymes, inflammatory cytokines, and proteins show similarity with those included in the gut microbiome. These findings have become available through newer artificial intelligence (AI) algorithms allowing big data analysis. From an evolutionary point of view, these pieces of evidence explain the strict and sophisticated interaction at the basis of human metabolism and immunity regulation in humans. They unravel more and more physiopathologic pathways included in human health and disease. DISCUSSION Several lines of evidence also obtained through big data analysis support the bi-directional role of gut microbiome and human genome in host metabolism and immune system regulation.
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The Use of Pictograms in the Evaluation of Functional Abdominal Pain Disorders in Children.
de Bruijn, CMA, Rexwinkel, R, Vermeijden, NK, Hoffman, I, Tack, J, Benninga, MA
The Journal of pediatrics. 2023;:113647
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Abstract
OBJECTIVE To evaluate whether the use of pictograms improves symptom evaluation for children with functional abdominal pain disorders (FAPDs). STUDY DESIGN This survey study was conducted in 2 academic centers and included patients aged 8-18 years visiting the outpatient clinic for FAPD symptom evaluation. Patients were randomized to fill out the questionnaire without or with accompanying pictograms to assess gastrointestinal symptoms. Afterwards, patients underwent clinical health assessment by the healthcare professional (HCP). Subsequently, the HCP filled out the same questionnaire without pictograms, while blinded to the questionnaire completed by the patient. Primary outcome was the level of agreement between identified symptoms as assessed by patients and HCP. RESULTS We included 144 children (questionnaire without accompanying pictograms [n = 82] and with accompanying pictograms [n = 62]). Overall agreements rates were not significantly different (without pictograms median, 70% vs with pictograms median, 70%). Accompanying pictograms did not significantly improve the assessment of abdominal pain symptoms. Accompanying pictograms were beneficial for concordance rates for nausea and vomiting symptoms (without pictograms median, 67% vs with pictograms median, 100%; P = .047). Subgroup analyses for children aged 8-12 years of age revealed similar results (concordance on the presence of nausea and vomiting without pictograms median, 67% vs with pictograms median, 100%; P = .015). Subgroup analyses for children ages 12-18 years showed no significant differences in concordance rates. CONCLUSIONS Pictograms do not seem to improve the assessment of FAPDs. However, the use of pictograms improves the evaluation of nausea and vomiting, especially for children aged 8-12 years. Therefore, HCPs could consider using pictograms in that setting during consultations.
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Do prokinetic agents provide symptom relief through acceleration of gastric emptying? An update and revision of the existing evidence.
Goelen, N, Jones, M, Huang, IH, Carbone, F, Janssen, P, Tack, J
United European gastroenterology journal. 2023;(2):146-162
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BACKGROUND Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions. OBJECTIVE To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis. DESIGN Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials. RESULTS Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub-optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta-analysis methodology. CONCLUSIONS The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated.
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Principles and clinical methods of body surface gastric mapping: Technical review.
O'Grady, G, Varghese, C, Schamberg, G, Calder, S, Du, P, Xu, W, Tack, J, Daker, C, Mousa, H, Abell, TL, et al
Neurogastroenterology and motility. 2023;(10):e14556
Abstract
Chronic gastric symptoms are common, however differentiating specific contributing mechanisms in individual patients remains challenging. Abnormal gastric motility is present in a significant subgroup, but reliable methods for assessing gastric motor function in clinical practice are lacking. Body surface gastric mapping (BSGM) is a new diagnostic aid, employs multi-electrode arrays to measure and map gastric myoelectrical activity non-invasively in high resolution. Clinical adoption of BSGM is currently expanding following studies demonstrating the ability to achieve specific patient subgrouping, and subsequent regulatory clearances. An international working group was formed in order to standardize clinical BSGM methods, encompassing a technical group developing BSGM methods and a clinical advisory group. The working group performed a technical literature review and synthesis focusing on the rationale, principles, methods, and clinical applications of BSGM, with secondary review by the clinical group. The principles and validation of BSGM were evaluated, including key advances achieved over legacy electrogastrography (EGG). Methods for BSGM were reviewed, including device design considerations, patient preparation, test conduct, and data processing steps. Recent advances in BSGM test metrics and reference intervals are discussed, including four novel metrics, being the 'principal gastric frequency', BMI-adjusted amplitude, Gastric Alimetry Rhythm Index™, and fed: fasted amplitude ratio. An additional essential element of BSGM has been the introduction of validated digital tools for standardized symptom profiling, performed simultaneously during testing. Specific phenotypes identifiable by BSGM and the associated symptom profiles were codified with reference to pathophysiology. Finally, knowledge gaps and priority areas for future BSGM research were also identified by the working group.