Introduction

Salmonella Enteritidis, a Gram-negative bacterium, poses a significant threat to gastro-intestinal health, often leading to widespread outbreaks. Acute gastroenteritis increases the likelihood of developing a disorder of gut brain interaction (DGBI), such as irritable bowel syndrome (IBS) and functional dyspepsia (FD). This study investigates the long-term risk of DGBI development 30 years post-Salmonella exposure and explores additional predictive factors.

Aims & Methods

In 1994 a Salmonella Enteritidis outbreak involved 36 schools in Bologna, 1811 individuals tested positive for this bacterium in stool cultures. Following this event, a prospective cohort study was initiated after 30 years. 300 subjects were randomly selected and assessed for DGBI prevalence using Rome III and Rome IV questionnaires, persistent gastrointestinal symptoms via the Gastrointestinal Symptoms Rating Scale (GSRS), anxiety and depression levels with the Hospital Anxiety and Depression Rating Scale (HADS), and quality of life using the SF12 questionnaire (12 item short form). The exposed group comprised 150 people who contracted S. Enteritis infection in 1994, while the control cohort consisted of individuals, matched for sex, age and geographic origin, who had not experienced a bacterial gastroenteritis. The DGBI course was estimated by comparing our results with a previous follow-up carried out in 2009.

Results

Questionnaires were completed by 175 subjects (58,3%, 88 cases and 87 controls). Among the exposed subjects 39.8% developed IBS and 34.1% FD compared to 6.9% IBS and 4.6% FD in the control group (p=<0.001). Multivariate logistic regression in the study population revealed predictive factors for IBS: S. Enteritidis infection [Odd Ratio (OR) 7.056, 95% CI 2.684-18.554, p=<0.001] and anxiety level evaluated in 2024 (OR 1.244, 95% CI 1.105-1.400, p=<0.001). Similarly, predictors for FD included S. Enteritidis infection (OR 10.218, 95% CI 1.259-82.925, p=0.03), anxiety level assessed in 2009 (OR 1.212; 95% CI 1.058-1.390, p=0.006), and Mental component summary (MCS) score (OR 0.047; 0.002-0.985; p=0.049). Notably, anxiety level evaluated in 2024 was predictive of IBS development in the exposed group, while anxiety level in 2009, along with MCS score, was predictive for FD. We found an increased IBS and decreased FD occurrence in 2024 compared to 2009 follow-up. Exposed individuals exhibited a statistically significative higher rates and severity rates of gastrointestinal symptoms in the following areas: abdominal pain, hunger pains, diarrhea, loose stools, urgency, rumbling bloating, constipation, hard stools and incomplete emptying. Psychiatric comorbidities resulted more common in exposed group than in non-exposed one, in particular anxiety evaluated in 2024 (31.8% vs 10.3%, p=0.002). The exposed group showed lower scores in all SF12 subcategories compared to the control group.

Conclusion

This study, following a 1994 foodborne culture-proven S. Enteritis outbreak, highlights that a bacterial gastroenteritis is a major risk factor for IBS and for FD even after 30 years from the infection.

Introduction

Patients with celiac disease (CD) can present persistence or de-novo occurrence of gastrointestinal (GI) symptoms later in life even following a strict gluten-free diet (GFD). Indeed, GFD can alter the gut microbiota inducing dysbiosis that with time may lead to the development of disorders gut-brain interaction (DGBI).

Aims & Methods

In this prospective study, we evaluated the rate of irritable bowel syndrome (IBS), functional dyspepsia (FD), anxiety, and depression over a follow-up period of more than 10 years in a population of patients with CD following GFD.
Patients with CD diagnosed between 2004 to 2014 at the University Hospital in Modena, Italy were re-evaluated to assess the presence of DGBI. Rome-IV (pediatric modules if patients were younger than 17 years old), gastrointestinal symptoms rating scale (GSRS) and hospital anxiety and depression scale (HADS) questionnaires were administered along with the evaluation of the last blood examinations. The rates of IBS, FD, anxiety, and depression were then assessed. Univariate and multivariate analyses were performed to investigate the presence of factors associated with IBS and FD.

Results

We contacted 197 patients out of 340 from our original pediatric cohort. Patients who were not strictly adhering to GFD (25 patients) and who did not complete the questionnaires (20 patients) were excluded from the study. The median follow-up time was 154 months (inter-quartile range 125-180). The rate of IBS was 14.47% (22/152) which increased to 22.3% (21/94) considering only the adult population (Table 1 panel A). Patients were then subclassified in IBS-C (5/22, 22.7%), IBS-M (6/22, 27.3%) and IBS-D (10/22, 45.5%). The overall rate of FD was 7.24% (11/152) (Table 1 panel B) and up to 11.7% (11/94) in the adult population and none in the pediatric one. We found that postprandial distress syndrome (PDS) was present in 7.89% (12/152) of the population and epigastric pain syndrome (EPS) in 5.26% (8/152). Significantly higher rates of anxiety were found in patients developing IBS and FD (Table 1 and 2). Univariate and multivariate analyses showed that a longer follow-up time was significantly correlated with a higher rate of IBS and that anxiety was correlated with both IBS and FD diagnosis (Table 1).

Conclusion

Over more than 10 years from the initial diagnosis of CD, we found a higher rate of IBS and FD than the one reported for the general population. In our cohort, DGBIs are correlated with higher levels of anxiety and longer follow-up time.

Disclosure

None

Introduction

Irritable bowel syndrome (IBS) is a multifactorial disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. The pathophysiology of IBS involves alterations in the epithelial barrier, but data on the intestinal vascular barrier are lacking.

Aims & Methods

The aims of this study were to investigate the morpho-functional integrity of the vascular barrier and to correlate barrier dysfunction with IBS symptoms. Forty-eight healthy subjects (AC) and 144 patients with IBS (61 IBS-D, 51 IBS-C and 32 IBS-M) were enrolled in the study. Rome IV criteria, Bowel disease questionnaire, Short Form 12, Hospital Anxiety Depression Scale were used to phenotype patients. Immunohistochemistry, western blot and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing two markers: plasmalemma vesicle–associated protein-1 (PV1) and vascular endothelial cadherin (VEC). A translational model based on HUVEC was used to evaluate permeability changes induced by mediators spontaneously released by mucosal biopsies, and to highlight the underlying molecular mechanisms. Correlation analyses between experimental and clinical data were performed.

Results

Mucosal vessel density was significantly increased by 1.5 fold in the colonic mucosa of IBS patients compared to AC (P<0.01). PV1 expression was increased (P<0.01) while VEC expression was decreased in the colonic mucosa of IBS patients compared to AC (P<0.05). Compared to AC, IBS mucosal mediators increased permeability in the HUVEC monolayer through the activation of protease-activated receptor (PAR)-2 and histone deacetylase (HDAC)11, resulting in VEC downregulation. PV1 expression significantly correlated with anxiety and depression scores and health-related quality of life reported by IBS patients.

Conclusion

The vascular barrier is impaired in IBS and contributes to clinical manifestations

Introduction

Individuals with Disorders of Gut-Brain Interaction (DGBI) may experience avoidant/restrictive food intake disorders (ARFID). However, these findings have been limited to specialist neurogastroenterology clinics. We assessed the association between ARFID and DGBI within the adult general population.

Aims & Methods

A population-based Internet survey with pre-defined demographic quotas was conducted across the UK and USA in 2023. The survey included the Rome IV diagnostic questionnaire for DGBI, the nine-item ARFID screen (NIAS), and questions regarding demographics, body mass index, non-GI somatic symptoms, anxiety and depression, quality of life, and healthcare utilisation.

Results

4002 adults (mean age 47 [range 18-91] years, 50% females) completed the survey, of whom 1704 (42.6%) had symptoms compatible with at least one DGBI.
The prevalence of ARFID-positive screens was significantly higher among participants with DGBI compared to those without DGBI (34.6% vs. 19.4%, OR 2.2), with similar findings noted in each country. Among participants with DGBI, positive ARFID screens by NIAS subscale were poor appetite (21.5%), picky eating (18.1%) and a fear of aversive consequences (9.9%).
ARFID was present in 42.1% of those with oesophageal DGBI, 49.2% with gastroduodenal DGBI, 33.1% with bowel DGBI, and 41.8% with anorectal DGBI. The presence of ARFID among the two widely investigated DGBI, i.e. functional dyspepsia and IBS, was 56.2% and 50.4%, respectively.
The presence of ARFID increased with the number of DGBI regions, ranging from 19.4% in those with no DGBI, 27.5% with DGBI in one region, 40.0% for DGBI in two regions, 49.7% for DGBI in three regions, and 61.1% for DGBI in four regions (p<0.001). A positive correlation was seen between the number of DGBI regions and the severity of ARFID (r=0.29, p<0.001).
Individuals with DGBI plus ARFID, compared to those with only DGBI, were significantly more likely to be underweight (7.9% vs. 1.5%), have greater non-GI somatic symptoms and mood disturbances, reduced mental and physical quality of life, and increased GI healthcare visits; all p<0.001.

Conclusion

Positive ARFID screens are common in DGBI and associated with increased general health burden. Routine screening for ARFID in DGBI will inform the multi-integrated care plan provided by clinicians, dietitians, and psychologists.

Disclosure

Nil

Introduction

Irritable bowel syndrome (IBS) is a complex multifactorial disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Patients with IBS often complain of extra-intestinal symptoms resulting in impaired related quality of life. Growing evidence support the hypothesis that intestinal barrier dysfunction has a central role in the pathophysiology of IBS being the interface between the gut lumen and the deeper intestinal layers as well as the brain.

Aims & Methods

The aims of this study were: to characterize the epithelial and vascular barriers; to correlate molecular, morphological and functional aspects of epithelial and vascular barriers with IBS symptoms. 66 healthy subjects (AC) and 223 patients with IBS (112 IBS-D, 58 IBS-C and 53 IBS-M) were enrolled in the study. Rome IV criteria, Bowel disease questionnaire, Short Form 36, Hospital Anxiety Depression Scale were used to phenotype patients. Sugar test was used to evaluate in vivo permeability. The vascular barrier was characterized by using immunohistochemistry, western blot and electron microscopy. Vascular permeability was evaluated by assessing two markers: plasmalemma vesicle–associated protein-1 (PV1) and vascular endothelial cadherin (VEC). A translational model based on Caco-2 cells or HUVEC was used to evaluate permeability changes induced by mediators spontaneously released by mucosal biopsies and to highlight the underlying molecular mechanisms. Correlation analyses have been performed among experimental and clinical data.

Results

Compared to AC, lactulose (P<0.05), sucralose (P<0.01), sucrose (P<0.01) excretion and the L/M ratio (P<0.01) were significantly increased in IBS patients. Soluble mediators released by mucosal biopsies of IBS patients increased Caco-2 permeability compared to AC mediators (P<0.05) via a down-regulation of tight junction gene expression. Blood vessels were significantly increased by 1.5 fold in the colonic mucosa of IBS patients compared to AC (P<0.01). PV1 expression was increased (P<0.01) while VEC expression was decreased in the colonic mucosa of IBS group compared to AC (P<0.05). IBS mucosal mediators increased HUVEC permeability compared to AC mediators. The HUVEC changes associated with IBS samples were mediated by a protease-activated receptor (PAR)2 dependent mechanism resulting in VEC down-regulation. Significant correlations emerged among permeability changes and intestinal, extra-intestinal symptoms and health-related quality of life reported by IBS patients.

Conclusion

Epithelial and vascular barriers are compromised in IBS and are likely involved in symptom development.

Disclosure

Nothing to disclose