BACKGROUND Irritable Bowel Syndrome (IBS) is heterogenous disorder of gut-brain interaction, with a key role for the dysregulated host-gut microbiota interplay. IBS subtyping is based only on symptoms of bowel habits, reflecting limited insight into underlying biological mechanisms. Aims: This study aimed to define microbiota-based IBS phenotypes and to compare these to traditional stool-based subtyping. Methods: The study utilised data from the Maastricht IBS cohort. Gut microbiota composition was analysed using shotgun metagenomic sequencing. Faecal volatile organic compounds (VOCs) were measured by gas chromatography mass spectrometry. Dietary intake and gastrointestinal and mental health symptoms were assessed using a food frequency questionnaire, the Dutch Healthy Diet-15 index, the Gastrointestinal Symptom Rating Scale, and Hospital Anxiety and Depression scores, respectively. Machine-learning approaches were applied to identify microbiota-based phenotypical clusters, which were compared with established Rome III subtypes, and associated with faecal VOCs, gastrointestinal symptom severity, diet and mental health. Results: 178 IBS patients and 134 healthy controls were included. Gut microbiota composition distinguished IBS patients from healthy controls with an AUCROC 0·8. This discriminatory profile was not associated with Rome III subtypes, while statistically significant associations were found with faecal VOCs profiles (i.e. R=0·67, p=4·46e-4) and symptom severity scores of abdominal pain (p=0·05), reflux (p=0·03), and diarrhoea (p=0·01) and depression (p<0·001). Dietary associations varied across clusters. Conclusion: These results suggest that gut microbiota profiling might provide a basis to define relevant IBS endotypes. Further exploration and validation efforts into this direction are needed using longitudinal studies to refine IBS patient stratification ultimately. .

ABSTRACT Introduction Visceral hypersensitivity (VHS) is considered a hallmark of irritable bowel syndrome (IBS) characterized by altered thresholds for rectal pain and discomfort during rectal distention. Rectal distention can also elicit the urge to defecate, a normal physical sensation that is, reported more often in IBS and may involve mechanisms distinct from pain and discomfort. This study investigates clinical, psychological, and physiological correlates of increased urge to defecate in IBS compared with healthy controls (HC), including sex‐based differences. Methods Patients with IBS (Rome III criteria) and HC underwent rectal balloon‐distension and completed questionnaires on demographics, lifestyle, gastrointestinal (GI) and psychological symptoms, and health‐related quality of life (HrQoL). Latent clusters were identified using finite‐mixture modeling, and associated determinants were evaluated using multivariable logistic regression analyses. Results Among 322 participants (220 IBS, 102 HC), the occurrence of the urge to defecate was more frequent in IBS than in HC (80.9% vs. 51.9%; p < 0.001) and often co‐occurred with rectal pain and discomfort, particularly in patients with VHS. Latent class analysis identified three clusters, primarily distinguished by rectal symptom‐distribution, with the most symptomatic cluster showing greater GI‐symptom severity, higher psychological burden, and lower HrQoL (all p < 0.001). Regression analyses confirmed associations of urge with GI symptom severity, depressive symptom scores, and co‐occurrence of pain/discomfort, but no association was found based on IBS subtype or sex. Conclusion Increased urge to defecate is highly prevalent in IBS, strongly associated with rectal pain, rectal discomfort, psychological burden, and reduced HrQoL, but not in the IBS subtype, suggesting shared or overlapping mechanisms, particularly in the context of VHS. These findings underscore its clinical and pathophysiological relevance, supporting its value for patient‐phenotyping and tailored management. Trial Registration The Maastricht Irritable Bowel Syndrome (MIBS) cohort study was registered under the registration number NCT00775060

Older adults represent a rapidly expanding subgroup of patients with inflammatory bowel disease, yet they remain markedly under-represented in pivotal clinical trials, limiting age-specific estimates of drug benefit and harm. This review synthesises the available evidence on the influence of ageing on the pharmacology, efficacy and safety of orally administered targeted inflammatory bowel disease therapies, focusing on registered Janus kinase inhibitors (tofacitinib, upadacitinib, filgotinib) and sphingosine-1-phosphate receptor modulators (ozanimod, etrasimod). Because the available age-stratified evidence is sparse and heterogeneous, a narrative review methodology was chosen to map the literature and identify knowledge gaps. We pragmatically report age-related findings using the age cut-offs applied in original studies and map outcomes including clinical and endoscopic response/remission, corticosteroid sparing and adverse drug events of special interest (serious/opportunistic infections, cardiovascular and thromboembolic events, malignancies and treatment discontinuation). Across the limited age-stratified datasets, efficacy appears largely maintained in older patients, but the evidence base is heterogeneous and frequently lacks dedicated analyses. Ageing-related physiological changes, comorbidity, frailty and polypharmacy are expected to modulate pharmacokinetic and pharmacodynamic variability and to amplify the clinical relevance of class-specific safety concerns, particularly infections, major adverse cardiovascular events and malignancy signals with Janus kinase inhibition and initiation-related cardiovascular/conduction considerations with sphingosine-1-phosphate modulation. There is, however, no clear consensus on how ageing-related vulnerability, including frailty and comorbidity burden, should be defined, measured, and reported across studies, which complicates the interpretation and comparison of outcomes. In the absence of robust outcome data for older adults with inflammatory bowel disease, treatment selection should be guided by biological vulnerability (frailty, organ function, comorbidity burden) and structured risk-mitigation strategies, while future research should prioritise age- and frailty-enriched prospective studies with geriatric-relevant outcomes and long-term pharmacovigilance.

Evidence suggests psychological factors including personality traits can have impact on the development and course of irritable bowel syndrome (IBS) and associated health‐related quality of life (HrQoL), with large individual heterogeneity. Main aim of this study was to examine between‐persons associations and within‐sample concurrent associations of the personality traits neuroticism, extraversion, conscientiousness, openness and agreeableness with gastrointestinal (GI) symptoms, psychological factors and HrQoL in IBS‐patients.

BACKGROUND One Class Modelling (CM) is popular among chemometricians, but not well known among omics scientists in general. One issue is that typical CM approaches, including SIMCA, often result in unsatisfactory results due to e.g. large variation, centring and scaling issues, sparsity, outliers, and non-linearities in typical omics data. These effects can cause an inflated decision boundary (of the target class), thereby returning many false positives (of non-target cases). Tree-based techniques are by nature resistant to these challenges. In this study we explore tree-Based SIMCA variants in omics scenarios and compare to existing strategies. RESULTS We present a non-linear form of SIMCA by making use of sample proximities obtained through Unsupervised Random Forest and Isolation Forest (termed URF-SIMCA and IF-SIMCA). We compare accuracy of the algorithms with (traditional) SIMCA, one-class support vector machines, and isolation forest. This comparison was based on five (previously published) clinical omics datasets and the wine-dataset. URF-SIMCA showed superior behaviour. Using the pseudo-sampling principles, an interpretation could be made on the important features for the separation between the target and non-target classes. Using the wine-dataset, we empirically show that these directly relate to information obtained through two-class algorithms. Moreover, feature trajectories in the score- and orthogonal distance spaces further enable interpretability of the model. SIGNIFICANCE URF-SIMCA offers an easy to use extension of SIMCA, which deflates the variance of the target class, allowing for better separation. The increased modelling performance comes at the cost of feature interpretation, but this can be tackled using the pseudo-sampling principle.

Gastrointestinal (GI) motility disorders are characterized by abnormalities in the motor functions of the GI tract. The diagnostic evaluation of these disorders frequently involves invasive and time-consuming examinations, for which access may be limited. Volatile organic compounds (VOCs) could serve as non-invasive alternative. Therefore, the aim of this study was to explore the potential of exhaled breath VOCs as biomarkers in patients with GI symptoms and potential GI motility disorders. In this exploratory, prospective study, breath samples were obtained from patients undergoing ambulatory motility tests as part of routine clinical care. VOCs in exhaled breath were assessed using thermal desorption chromatography-mass spectrometry (TD-GC-MS). The resulting data were subsequently pre-processed and analyzed using machine learning approaches. Hundred participants were included in the analysis, of whom 67 were women (67%), with a median age of 56.5 years (IQR: 29.8). The diagnostic work-up comprised 55 gastric emptying tests, 55 high-resolution esophageal manometries, 3 antroduodenal manometries, and 1 colon manometry. These examinations resulted in 48 motility disorder diagnoses, while 51 patients showed no evidence of motility abnormalities. Fifteen VOCs were identified as most discriminative markers for the presence or absence of GI dysmotility, with a sensitivity of 75%, and specificity of 60%. VOCs in exhaled breath show promise to distinguish patients with GI motility disorders from those without, in a population of patients with GI symptoms. Future research is warranted to further refine and validate these results in a larger cohort and to explore the diagnostic performance of VOCs in specific subtypes of motility disorders.

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. We profiled faecal headspace VOCs in a cohort of 164 patients with IBS and 143 healthy controls using gas chromatography-mass spectrometry. 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. 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 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. This study highlights the potential of faecal VOC profiling as a non-invasive tool for studying and characterizing 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 personalized therapeutic strategies.

Abstract 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.