Background:Irritable Bowel Syndrome (IBS), a disorder of gut-brain interaction, is diagnosed using symptom-based Rome criteria. These criteria classify IBS patients into four subtypes in accordance to their stool patterns. However, whether this subtyping approach is based on true differences in the underlying biology of IBS patients, is unclear. Volatile organic compounds (VOCs) in the faecal headspace reflect both the gut microbial and host intestinal intraluminal processes and thereby may be used to study pathophysiological differences between IBS and its subtypes. Methods:We profiled faecal headspace VOCs in a cohort of 164 patients with IBS and 143 healthy controls using gas chromatography-mass spectrometry (GC-MS). Random forest models were employed to impute missing values and identify discriminatory VOCs to differentiate IBS patients from healthy controls. We corrected for faecal water content using Partial Least Squares Regression. Multivariate associations between the obtained volatile profiles and Rome III IBS subtypes were evaluated using regularized MANOVA. Results:A total of 39 VOCs, including short-chain fatty acid esters, neurotransmitter-related metabolites, alcohols, and sulphides, were selected as significantly altered in patients with IBS. Our classification model achieved an area under the curve (AUC) of 0.82 on both training and independent test sets, demonstrating robust separation between IBS patients and healthy individuals. However, VOC profiles did not associate to Rome III -based IBS subtypes. Conclusion:This study highlights the potential of faecal VOC profiling as a non-invasive tool for studying and characterising IBS, yet they also reveal a disconnect between metabolic signatures and current stool-based subtypes. While the Rome criteria remain the clinical standard for diagnosis and subtyping of IBS, they offer limited insight into underlying disease mechanisms. Future research should focus on integrating VOC analysis with other omics approaches to refine IBS sub-classification into biologically relevant clusters, which may aid to improve personalised therapeutic strategies.

BACKGROUND Inflammatory bowel disease (IBD) may negatively affect health-related physical fitness. However, the development of interventions to improve health-related physical fitness and thereby disease outcomes is hindered by insufficient evidence. This study compared health-related physical fitness between patients with IBD and healthy control subjects, examined associations with disease and treatment characteristics, and explored patients' perspectives. METHODS In this cross-sectional study, 105 patients with IBD and 102 age- and sex-matched healthy control subjects performed validated tests for body fat (4-site skinfold thickness), cardiorespiratory fitness (steep ramp test), muscular strength (steep ramp test, 60-second sit-to-stand test, hand-held dynamometry), muscular endurance (isokinetic dynamometry), and flexibility (sit-and-reach test). Data on disease and treatment characteristics, fatigue, physical activity, and patients' perspectives were collected. RESULTS Patients with IBD had higher body fat (29.5% vs 26.9%; P = .012), lower steep ramp test performance (peak work rate 4.2 W/kg vs 4.8 W/kg; P < .001), fewer sit-to-stand repetitions (42 vs 47; P = .002), and reduced hamstring strength (3.0 N/kg vs 3.2 N/kg; P = .011) compared with healthy control subjects. This was associated with higher age, female sex, higher body mass index, fatigue, arthritis, and multiple biologicals used. Most patients considered physical fitness important and beneficial for their symptoms, and the majority expressed interest in professional support. CONCLUSIONS Patients with IBD have higher body fat and reduced cardiorespiratory fitness and muscular strength compared with healthy control subjects. Especially, patients with a higher age, female sex, higher body mass index, fatigue, arthritis, or multiple biologicals used are at risk for such impairments and may benefit from physical exercise interventions.

Disorders of gut–brain interaction (DGBI) affect up to 40% of people worldwide and in several studies an association with hypermobility spectrum disorders (HSD) was described. HSD patients frequently report gastrointestinal (GI) symptoms and GI dysmotility has been suggested as underlying mechanism. This study evaluates whether individuals with (undiagnosed) joint hypermobility and/or HSD show different GI symptom and motility patterns compared to those without hypermobility/HSD. In this prospective open-label study, patients who were referred for GI motility assessment between 2016 and 2018 were included. Motility assessments included esophageal manometry, gastric emptying test, antro-duodenal manometry, colonic manometry, and/or a colonic transit study. Joint hypermobility was assessed using the Beighton score, and HSD was diagnosed using the Brighton criteria. Symptom severity, anxiety and depression, and quality of life were evaluated through validated questionnaires. Eighty-seven participants were included (73 women, median age 42.0 years), and categorized into HSD (n = 23) and non-HSD (n = 64), with further subdivision by Beighton cut-off values (≥ 4, and ≥ 6). GI symptom scores were high, with 37% of the total population exhibiting depressive symptoms (HADS ≥ 8), and 32% experiencing anxiety. Quality of life scores were generally low, with a physical composite score of 26.9 (13.2) and a mental composite score of 47.3 (17.1). Across all comparisons, no significant differences in GI symptoms or motility patterns were found between all groups. This exploratory tertiary care study found no distinct GI symptom or dysmotility patterns between patients with and without hypermobility/HSD. Further research is warranted to investigate whether GI dysmotility is related to hypermobility.