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

Helicobacter pylori infection affects approximately half of the global population and may lead to sever complications, including gastric cancer. Current antibiotic-based therapies face the challenge of rising resistance rates. Therefore, there is urgent medical need for an effective vaccine. Despite extensive research efforts, no H. pylori vaccine has yet made it to clinical application. Aim of our study is the development of a novel multi-epitope-based H. pylori vaccine

Aims & Methods

Sixteen selected B- and T-cell epitopes from six key virulence factors were fused to create the Multi-Epitope-Unit (MEU) antigen. Two vaccine formulations were evaluated: MEU combined with flagellin as adjuvant, and MEU incorporated into the Modified Vaccinia virus Ankara (MVA) genome for enhanced antigen delivery. The efficacy was assessed in murine models using H. pylori SS1 infection, with evaluation in both prophylactic and therapeutic settings. To explore the possible clinical relevance, crude antigens from 48 human clinical isolates of H. pylori obtained from international healthcare centers were tested for binding capacity with anti-MEU antibodies generated from immunized mice.

Results

Both vaccine formulations elicited robust MEU-specific antibody and CD4+ T-cell responses. The vaccines generated a balanced Th1/Th2 immune response profile and significantly elevated CD4+NKT-like cell levels. Complete bacterial clearance was achieved with protein-based vaccination followed by MVA boost or two doses of MVA vaccine in both prevention and treatment models. Binding assays revealed that anti-MEU antibodies demonstrated positive binding capacity to crude antigens from all 48 tested human clinical isolates (100% reactivity), confirming broad-spectrum recognition across diverse H. pylori strains from different geographical origins.

Conclusion

This study represents groundbreaking research, presenting a novel promising H. pylori vaccine candidate. The comprehensive testing against 48 human clinical isolates from international healthcare units provides unprecedented evidence of functional immune responses. Our data demonstrate 100% binding reactivity of anti-MEU antibodies to crude antigens from ALL tested clinical isolates, representing diverse geographical origins and strain variations. This finding demonstrates for the first time that a H. pylori vaccine can generate immune responses effective against a vast spectrum of human pathogenic strains, which has eluded all previous vaccine approach failures and poses high expectation for a successful clinical application. Our multi-epitope vaccine represents a novel H. pylori vaccine development, being the first to demonstrate both complete bacterial clearance in preclinical models as well as a broad-spectrum reactivity against human clinical isolates. These results provide strong scientific rationale for advancing to toxicology studies and clinical evaluation, offering the first genuine hope for both prevention and treatment of H. pylori infections in human populations worldwide.

Disclosure

BK, HM and VW are employed by Iguana Biotechnology. The remaining authors declare no conflicts of interest.