Introduction

Avoidant/restrictive food intake disorder (ARFID) is characterized by reduced dietary intake leading to medical and/or psychosocial impairment, independent of body image concerns. Its prevalence in gastrointestinal (GI) disorders remains unclear despite frequent symptom-induced restrictive eating behaviors.

Aims & Methods

We aim to assess the prevalence and characteristics of ARFID in patients with various GI disorders compared to healthy volunteers (HV), and its associations with symptom severity, extraintestinal somatic symptoms and depression.
Data from 92 HV and 467 GI patients across seven tertiary care diagnostic categories —including irritable bowel syndrome (IBS, n=88), functional dyspepsia (FD, n=83), (refractory slow transit) constipation (n=59), reflux (n=107), globus (n=45), (non-obstructive) dysphagia (n=37), and achalasia (n=48)—were analyzed. Questionnaires included Rome IV criteria, ARFID screening, extraintestinal symptoms and depression scores (PHQ-12/9). Positive NIAS screening (NIAS+) was defined as meeting any subscale cutoff (≥10 for Picky Eating, ≥9 for Appetite, and ≥10 for Fear). Medical and/or psychosocial impairment in NIAS+ individuals was evaluated using the ARFID DSM-5 checklist. ARFID+ was defined as NIAS+ plus DSM-5 impairment. Odds ratios were calculated using a multiple logistic regression model with three-level hierarchical approach. Odds of fulfilling ARFID or NIAS criteria between DGBI diagnoses (step 1) were adjusted for z-scores of symptom severity (step 2) and extra-intestinal somatic symptoms and depression (step 3). Esophageal and non-esophageal disorders were analyzed separately.

Results

Table 1 shows demographics and characteristics of patients. Compared to HV, ARFID+ was significantly associated with IBS (OR: 15.00, p < 0.001), FD (OR: 10.59, p = 0.002), constipation (OR: 18.21, p < 0.001), dysphagia (OR: 7.03, p = 0.024) and reflux (OR: 5.16, p = 0.036), but not with achalasia and globus. Within disease categories, there were no differences in the odds of ARFID+ after adjusting for symptom severity (step 2) and for comorbid extraintestinal symptoms and depression (step 3). Increase in PHQ9, contributed independently to the presence of ARFID in non-esophageal disorders (OR: 1.11, p = 0.009).

Conclusion

ARFID symptoms are prevalent across various GI disorders. While mechanical factors may drive ARFID in esophageal conditions, psychological factors (e.g., depression) may play a role in ARFID in non-esophageal disorders. Further research is needed to establish the contribution of mechanical factors to ARFID in esophageal conditions. Routine ARFID screening is crucial to address psychosocial and nutritional impacts in GI patients.

Introduction

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut-brain interaction (DGBI), and bloating and visible abdominal distension are common symptoms among individuals with IBS and/or FD. Bloating refers to a subjective sensation of tension or pressure in the abdomen, which may or may not be reported together with visible abdominal distension. The underlying pathophysiological mechanisms may differ, with bloating suggested to be more related to hypersensitivity and visible abdominal distension to altered motility. The prevalence of these two symptoms in IBS and FD, especially as distinct symptoms, is not well known.

Aims & Methods

The aim was to investigate the link between bloating and distension with IBS and FD. Therefore, we performed a population-based internet survey of adults in the US, UK, and Mexico, including Rome IV IBS and FD diagnostic questions, somatization (PHQ-12), and psychological distress (PHQ-4). Four groups were created: those meeting the Rome IV criteria for IBS only, FD only, both IBS+FD, and a reference group including individuals without IBS, FD and organic diagnoses that could result in IBS- or FD-like symptoms. Within each group, we identified individuals who reported ≥weekly bloating alone (B), ≥weekly visible abdominal distension alone (D), ≥weekly combined B+D, or neither of both. The relationship between B, D and B+D in those with IBS and/or FD vs. the reference group was investigated using logistic regression models.

Results

The analysis included 5,448 participants (49.7% female; mean age 46.5 years, range 18-99), with 131 meeting criteria for IBS only, 360 for FD only, 217 for IBS+FD and 4,740 for the reference group. A larger proportion of individuals with IBS only (64.9%), FD only (50.6%), and especially those with IBS+FD (88.5%) reported bloating and/or visible abdominal distension compared to the reference group (13.7%). In the IBS only group, 16.0% reported bloating alone, 8.4% visible abdominal distension alone, and 40.5% combined bloating and visible abdominal distension. In the FD only group this was 12.8% (B), 8.9% (D), and 28.9% (B+D), and in the IBS+FD group 18.9% (B), 8.3% (D), and 61.3% (B+D), respectively. Reporting bloating alone or combined bloating and visible abdominal distension was strongly linked to fulfilling criteria for IBS only, FD only, and concomitant IBS+FD vs. the reference group, with weaker links for visible abdominal distension in the absence of bloating (Table). After adjusting for age, sex, BMI, psychological distress and somatization, the links persisted. The strongest association was observed between combined bloating and visible abdominal distension (vs. neither) and concomitant IBS+FD (vs. the reference group); adjusted odds ratio 28.6 [95%CI 17.6-46.6].

Conclusion

Bloating and visible abdominal distension as distinct and overlapping symptoms are strongly linked to IBS, FD, and concomitant IBS+FD in the general population. Assessing bloating and visible abdominal distension as separate symptoms may be important to enable individualized treatment for individuals with IBS and FD.

Introduction

The achievement of histological remission (HR) is a key treatment goal in ulcerative colitis (UC), as it is suggestive of better disease management and predicts response to therapy.
The absence of neutrophils in epithelium and lamina is crucial to define HR. However, the role of neutrophil number and localisation remains unclear. We aimed to develop a novel artificial intelligence (AI)-driven system to automate neutrophil detection, localisation, and quantification, supporting assessment of HR and enable the prediction of response to therapy.

Aims & Methods

We developed an AI-driven system by integrating two deep learning models to (1) segment whole slide images (WSIs) into epithelium, crypts and lamina propria and to (2) detect and quantify neutrophils. Outputs from these models were combined to compute neutrophil densities in the lamina propria, epithelium, and overall tissue. The optimal neutrophil density cut-offs to assess disease activity (Geboes score >2B.0) in UC patients were identified in the AMAC phase 2 Mirikizumab trial, and subsequently validated in the multicentre prospective PICaSSO cohort study. Cut-offs to determine treatment response at weeks 12 and 52 (histological improvement [HI; Geboes score ≤3.1] and histological remission [HR; Geboes score ≤2B.0]), were also evaluated.

Results

Table 1 shows the system diagnostic performance in assessing disease activity and predicting response to therapy at W12 and W52 in the Mirikizumab cohort.
303 WSIs from active UC patients from the multicentre, randomised, double-blind, parallel-arm, placebo-controlled phase 2 clinical trial of Mirikizumab were analysed. The model yielded a DICE SØrensen of 0.57 for segmentation, precision of 82.3% and recall of 77.0% for neutrophil detection. The system identified an overall optimal neutrophil density cut-off (cells/mm²) predictive of disease activity of >21.7.0 (>10.1 and >30.4 for epithelium and lamina propria, respectively), with an accuracy of 86% (85% and 85%, respectively). Further validation in the multicenter PICaSSO cohort yielded to similar results.
Moreover, the overall optimal cut-off to predict histological remission at W52 was <20.8 (<10.4 and <27.9 for epithelium and lamina propria, respectively), with an accuracy of 82.0% (81% and 80%, respectively).

Conclusion

Our novel AI-based system demonstrates strong potential as an automated tool to detect, localise, and quantify neutrophils to assess histological activity and predict response to therapy in a clinical trial UC cohort and real-world settings. This framework could be applied in clinical trials and routine clinical practice, offering objective guidance for personalised management in UC patients.

References

[1] Santacroce G, Meseguer P, Zammarchi I, et al. P406 A novel active learning-based digital pathology protocol annotation for histologic assessment in Ulcerative Colitis using PICaSSO Histologic Remission Index (PHRI). Journal of Crohn's and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i843–i844
[2] Graham S, Vu QD, Jahanifar M, et al. CoNIC Challenge: Pushing the frontiers of nuclear detection, segmentation, classification and counting. Med Image Anal. 2024;92:103047.

Disclosure

MI received research grants and consultant fees from Olympus, Pentax, Eli Lilly, and Janssen. All other authors declare no competing interests.

Introduction

Non-celiac gluten/wheat sensitivity (NCGWS) is characterized by gastrointestinal and extra-intestinal symptoms triggered by gluten/wheat ingestion. Symptoms of NCGWS overlap with those of irritable bowel syndrome (IBS) or functional dyspepsia (FD). Due to diagnostic challenges and symptom overlap, data on the prevalence and predictors of NCGWS among patients with IBS or FD, especially those with refractory symptoms, are limited.

Aims & Methods

This was a prospective, multicentric, double-blind, placebo-controlled, crossover trial conducted from October 2021 to March 2023 in India.This was prospectivly registered with the clinical trials Registry, INDIA (CTRI/2021/10/037323). Adults aged 18–65 years with Rome IV-defined irritable bowel syndrome (IBS) or functional dyspepsia (FD) refractory to standard treatment were enrolled after excluding celiac disease, wheat allergy, and alarm features. Participants underwent a two-step diagnostic protocol. In Step I, patients adhered to a 6-week strict gluten-free diet (GFD) under dietitian supervision. Weekly assessments of gastrointestinal and extra-intestinal symptoms, health-related quality of life (HRQoL), and psychological scores were performed using validated instruments. Gluten responders—defined by ≥30% reduction in one to three primary symptoms—were advanced to Step II: a randomized, double-blind, placebo-controlled gluten challenge with crossover. Subjects received indistinguishable gluten or placebo cookies (8 g/day) for one week, followed by a one-week washout and crossover. A ≥30% symptom difference between gluten and placebo phases confirmed non-celiac gluten/wheat sensitivity (NCGWS). Primary outcome was NCGWS prevalence; secondary outcomes included symptom and HRQoL changes post-GFD and predictors of NCGWS. Statistical analyses included intention-to-treat principles and multivariable regression to identify baseline predictors.

Results

Of the 252 patients screened, 177 were enrolled for 6-week GFD (step I), and 154 patients completed this phase (mean age 41.9±14.2 years, 53.2% males). Eighty two (52.3%) patients responded to GFD, of whom 77 entered step 2 (DBPCGC). Thirty one (20.1%) patients had significant symptom worsening on blinded gluten ingestion, suggesting the presence of NCGWS. Independent predictors of NCGWS were female gender, FD-IBS overlap, headache, fatigue, and anxiety. Significant improvements in gastrointestinal symptoms, health-related quality of life, and psychological scores were observed after GFD in responders. No significant impact of diet sequence was noted.

Conclusion