Added Value of 13C Analysis in Breath Tests in H2-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

INTRODUCTION: Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled 13CO2 after ingestion of 13C-lactose has been proposed to mitigate this problem. OBJECTIVE: The aim of the study was to assess the performance of measuring methane and 13CO2 in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test. METHODS: Individuals referred for lactose breath testing and healthy controls were included. Participants received 13C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and 13CO2 excretion was assessed. RESULTS: 151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20 ppm above baseline. In subjects with normal hydrogen excretion, cumulative 13C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10 ppm). CONCLUSIONS: In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of 13C-lactose with measurement of 13CO2 excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.

Nutrition and Disorders of Gut-Brain Interaction.

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.

Prevalence of delayed gastric emptying in patients with gastroparesis-like symptoms.

BACKGROUND: The European consensus defined gastroparesis as a condition characterised by delayed gastric emptying (GE) in the absence of mechanical obstruction, with a symptom pattern of predominant nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). The distinction between patients with gastroparesis and those with functional dyspepsia (FD), another gastrointestinal condition characterised by predominant PDS or epigastric pain syndrome symptoms, is ongoing. AIM: To investigate the extent that symptom patterns may differentiate gastroparesis from FD. METHODS: This retrospective study included 637 patients from Leuven University Hospital in 2006-2021 who had upper gastrointestinal symptoms, underwent a GE test, and completed the Dyspepsia Symptom Severity (DSS) questionnaire. Patients were identified as with gastroparesis-like symptoms (GPLS; i.e., moderate to severe nausea with moderate to severe PDS) or FD symptoms (not fitting GPLS). We excluded patients aged <18 years, and those with diabetes, organic gastrointestinal disease or a history of abdominal surgeries. Demographic and clinical variables were compared. RESULTS: Among 545 patients, 238 reported GPLS and 307 reported FD symptoms. Those with GPLS had a significantly higher prevalence of delayed GE (half emptying time (T1/2) ≥109 min) and lower body mass index than those with FD (33.2% vs 17.6%, p < 0.01; 19.9 vs 21.2, p < 0.01, respectively). Among GPLS patients, those with delayed GE had higher DSS than those without (13.0 vs 12.0, p < 0.01). CONCLUSIONS: In tertiary care patients who reported gastroparesis or FD symptoms, the presence of delayed GE was associated with GPLS. In patients with GPLS, delayed GE was associated with higher symptom severity.

Understanding and managing patients with overlapping disorders of gut-brain interaction.

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.

Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

BACKGROUND/OBJECTIVES: The global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real-world evidence of this gastroparesis-like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis. METHODS: In the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut-brain interaction via Internet. We selected subjects with gastroparesis-like symptoms (GPLS) (nausea and/or vomiting ≥1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self-induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global-10), symptoms of anxiety and depression (PHQ-4), somatic symptoms (PHQ-12), and healthcare utilization. RESULTS: The global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non-gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms. CONCLUSIONS: GPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption.

Zinc and gut microbiota in health and gastrointestinal disease under the COVID-19 suggestion.

Microelements represent an emerging resource for medicine and its preventive branch. Zinc is the second most abundant element in our organism with peculiar physiologic functions and pathophysiologic implications in systemic and gastrointestinal (GI) diseases. It interacts very often with gut microbiota (GM) and can affect natural course of GI diseases through a bidirectional relationship with intestinal bugs. We aimed to review literature data regarding zinc chemistry, role in health, and GI diseases in man with a special focus on its interaction with GM. We conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: zinc, microelements, gut microbiota, gut health, and COVID-19. Zinc has a rapid and simple metabolism and limited storage within our body. Its efficacy on immune system modulation reflects on improved response to pathogens, reduced inflammatory response, and improved atopic/allergic reactions. Zinc is also involved in cell cycle regulation (namely, apoptosis) with potential anti-cancerogenic effects. All these effects are in a "symbiotic" relationship with GM. Finally, zinc shows preliminary viral antireplicative effects. Zinc seems to gain more and more evidences on its efficacy in allergic, atopic and infectious diseases treatment, and prevention. COVID-19 can be the booster for research on future applications of zinc as perfect "postbiotic" in medicine.

The gastrointestinal tract in hunger and satiety signalling.

BACKGROUND: Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. METHODS: Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling. RESULTS: Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake. CONCLUSION: Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.

Adults with eosinophilic oesophagitis identify symptoms and quality of life as the most important outcomes.

BACKGROUND: Well informed patients who are in cohesive partnership with physicians and who have realistic expectations towards therapy are more likely to be adherent, which results in better disease control. AIM: To assess which therapy goals adults with eosinophilic oesophagitis consider relevant. METHODS: Following refinement during three focus groups, a study brochure and questionnaire were sent to 148 patients. Patients ranked the importance (five levels) of short-term (in the next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life (QoL), histologically-detected inflammation and fibrosis, endoscopically-detected inflammation, and stricture formation as well as achieving histological remission while asymptomatic. Patients' characteristics associated with treatment goals were identified using logistic regression. RESULTS: Of 109 respondents (mean age 43 years), 85 were men. Over 90% chose symptoms and QoL improvement as important short- and long-term therapy goals. A greater proportion attributed more importance to long-term reduction in endoscopic (90% vs 73%, P < 0.001) and histological (81% vs 62%, P = 0.002) inflammation, and histologically-detected fibrosis (79% vs 64%, P = 0.018) when compared to short-term reduction in these features. Patients (88%) ranked achieving histological remission while being asymptomatic as important. Gender, therapy use, education level, QoL, symptom severity, and history of dilation were associated with patients' choice of treatment goals. CONCLUSIONS: Patients attributed most importance to improvement in symptoms and QoL. Reduction in biological activity was judged less important, but more relevant in the long- compared to the short-term.