Introduction

Irritable bowel syndrome (IBS) is one of the most prevalent chronic disorders worldwide, with considerable social and economic burden. Gut microbiome impairment is one of the potential pathogenic pathways of IBS, especially in its post-infectious form (PI-IBS).
To date, untargeted therapeutic microbiome modulation (i.e. probiotics, antibiotics, FMT) has achieved conflicting results in patients with dysbiosis-associated chronic disorders, including IBS and PI-IBS,while the inter-individual variability and the plasticity of gut microbiome supports its personalized manipulation.
In this study we performed microbiome-profiling in order to have a precision, microbiome-based approach to PI-IBS.

Aims & Methods

This is a pilot prospective, single-center, case-control study. Our aim was to describe outcomes of targeted microbiome modulation, informed by gut microbiome testing, in patients with PI-IBS referred to our Microbiome clinic, compared with a control group including PI-IBS patients managed at our General Gastroenterology outpatient clinic. PI-IBS was diagnosed according to Rome IV criteria.
Cases included patients treated in our Microbiome Clinic according to their gut microbiome testing. At baseline visit, a commercial stool microbiome testing based on 16S rRNA sequencing was prescribed. After test results, each patient received a personalized treatment to target gut microbial defects. Specifically, in the presence of increased abundance of pathobionts, or overgrowth of non-symbiont taxa, we envisaged their direct suppression by nonabsorbable antibiotics (rifaximin, neomycin-bacitracin, paromomycin) or went for the increase of beneficial taxa to enable microbial competition against them, using pre- or probiotics. In the case of low α-diversity and/or decreased abundance of specific beneficial taxa we prescribed pre- and/or probiotics to upregulate them, depending on the specific defect. When relevant, based on their microbial profile, patients received antibiotics before pre- and/or probiotics.
Controls included patients managed at our General Gastroenterology outpatient clinic who received empirical treatment according to physician’s choice.
All patients were evaluated with the IBS symptom severity scale (IBS-SSS) at baseline and after the end of treatments (±7 days). Response to treatments was defined as decrease in IBS-SSS score ≥50 points.

Results

Overall, 33 patients (13 cases and 20 controls) were enrolled. The two populations were homogeneous in terms of IBS subtypes and baseline IBS-SSS scores. Overall, the type and duration of treatments did not differ significantly between the two groups. Traditional dietary advices for IBS, without specific nutritional counselling, were given in both groups.
All patients in the group of cases (100%) and 11 of 20 patients in the control group (55%) experienced treatment response (decrease in IBS-SSS score ≥ 50 points), with a significant difference between groups (p< 0.0001). The mean IBS-SSS score after treatments was 163 in cases and 231 in controls (p= 0.01). The mean reduction in IBS-SSS score was 167 in cases and 74 in the control group (p= 0.001). Compared with controls, cases experienced significantly lower IBS-SSS subscores after treatments for satisfaction of bowel habits (p= 0.03), bloating (p= 0.04) and quality of life (p= 0.009).

Conclusion

This pilot study represents the first microbiome-based and personalized approach to PI-IBS. Our preliminary findings suggest that targeted microbial modulation, informed by microbiome profiling, might be effective in managing PI-IBS

References

1. Porcari S, Ingrosso MR, Maida M, et al. Prevalence of irritable bowel syndrome and functional dyspepsia after acute gastroenteritis: systematic review and meta-analysis. Gut. 2024;73:1431-1440.
2. Goodoory VC, Khasawneh M, Black CJ, et al. Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis. Gastroenterology. 2023;165:1206-1218.
3. Ratiner K, Ciocan D, Abdeen SK, et al. Utilization of the microbiome in personalized medicine. Nat Rev Microbiol. 2024;22:291-308.
4. Porcari S, Mullish BH, Asnicar F, et al. International consensus statement on microbiome testing in clinical practice. Lancet Gastroenterol Hepatol. 2025;10:154-167.
5. Drossman DA, Hasler WL. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016;150:1257-1261.
6. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997;11:395-402.
7. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol. 2015;8:309-325.

Disclosure

None

Introduction

Inflammatory Bowel Diseases (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, mostly invasive, time-consuming, and expensive. The faecal biomarker can help to monitor the disease activity and therapeutic response by simple and non-invasively. Faecal Calprotectin (FC) is the gold-standard, but it has many disadvantages. We previously described that the correlation between the faecal Plasminogen activator inhibitor type 1 (PAI-1) (FP) level and the endoscopic activity and therapeutic response promote that it could be used as a novel non-invasive faecal biomarker in IBD diagnosis. Moreover, the faecal PAI-1 protein level is stable at room temperature and 4°C.

Aims & Methods

To observe the exact faecal biomarker potential, we aimed to define the FP level of IBD patients and subjects with other gastrointestinal (GI) diseases and compare it with the FC. Faecal samples were collected from 128 patients with IBD (CD-active: 18, CD-inactive: 10, UC-active: 20, UC-inactive: 10) and other GI diseases [colorectal cancer (CRC): 20, diverticulosis [DIV]: 21, irritable bowel syndrome [IBS]: 10, adenoma: 10) and 9 healthy subjects. ELISA method was applied to define FP level, and it was validated for stool samples by us and 0.5 ng/g PAI-1 level was defined as the cut-off value. For FC observation diagnostic FC ELISA kit (Orgentec) was used. 50 mg/g cut-off value was applied at FC. Confusion matrix analysis was utilized to define Youden-index, positive predictive value (PPV), negative predictive value (NPV), accuracy, specificity, and sensitivity of the measured values.

Results

FP level was significantly higher in patients with active IBD compared to inactive and non-IBD subjects (0.64 vs 0.0 ng/g, p<0.0001). No significant differences were observed between CD-active and UC-active groups (0.46 vs 0.79 ng/g, p=0.65). In addition, FP concentrations were significantly increased in active IBD (0.76 pg/g) patients compared to inactive IBD (0.0 pg/g, p=0.0001), CRC (0.11 ng/g, p=0.02), DIV (0.05 ng/g, p=0.001), IBS (0.0 ng/g, p<0.0001), adenoma (0.0 ng/g, p<0.0001), and healthy (0.0 ng/g, p=0.0002) subjects. However, FC showed the same pattern as FP, except at the CRC, adenoma and DIV. In these groups, there were no significant differences compared to the active IBD (487.4 mg/g) subjects (vs CRC: 147.1 mg/g, p=0.09; p=; adenoma: 159.8, p=0.056. Confusion matrix analysis defined high specificity (83.5%) and moderate sensitivity (57.9%) values (TP: 22, FP: 14, FN: 17, TN: 71, PPV: 0.61, NPV: 0.816) at the FP measurements. Nevertheless, at FC levels 35.3% specificity and 94.7% sensitivity were measured (TP: 36, FP: 55, FN: 2, TN: 30, PPV: 0.396, NPV: 0.938). Calculated Youden-index was higher at the FP (0.41) compared to the FC (0.3). On the other hand, the accuracy of the FP is 75.6% and the FC is 53.6%. Based on the results of all FP levels measured (N=299) so far, the calculated values were specificity: 78%, sensitivity: 62%, PPV: 0.63, NPV: 0.78, Youden-index: 0.4, accuracy: 72.3%.

Conclusion

Our results suggest that the FP level selectively increased in the active IBD and discriminated more specifically from the other GI diseases compared to the FC. However, the sensitivity was lower, but it was improved by the increasing patient numbers at the pooled FP levels. Thus, the FP level could be useful in the diagnosis of IBD independently or combined with FC.

References

Jójárt B, Resál T, Kata D, Molnár T, Bacsur P, Szabó V, Varga Á, Szántó KJ, Pallagi P, Földesi I, Molnár T, Maléth J, Farkas K. Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases. J Crohns Colitis. 2024 Mar 1;18(3):392-405. doi: 10.1093/ecco-jcc/jjad160. PMID: 37751311; PMCID: PMC10906952.

Introduction

Irritable bowel syndrome (IBS) has a profound impact on health-related quality of life. Increasing evidence suggests psychological factors have a large impact in the development and course of IBS, and in particular quality of life, with large individual heterogeneity. This observational study aims to investigate the influence of personality traits using the Big Five Inventory (BFI) and examine their associations with abdominal pain, general and gastrointestinal-specific anxiety, and quality of life in patients with IBS.

Aims & Methods

Data from a large observational study in patients with IBS (Rome III criteria) was used, in which patients completed questionnaires with regards to personality traits (BFI-44), symptom severity, general anxiety, GI-specific anxiety, and quality of life. Multivariable regression models and a network correlation analysis were used to determine underlying associations.

Results

194 patients were included for analysis (74.7% female, mean age 51.36 years). There was a positive association of neuroticism to GI-specific anxiety (B 7.234, P = 0.040) and general anxiety (B 0.954, P = 0.040) with a strong negative association to mental quality of life (B – 3.576, P = 0.007). In addition, a strong negative association of agreeableness to mental quality of life was found (B – 4.266, P = 0.001). Although there were no significant associations of personality traits to abdominal pain, positive associations were found regarding general anxiety (B 6.304, p < 0.001) and GI-specific anxiety (B 0.034, P <0.001) of abdominal pain. There were no associations found with regards to the other personality traits openness, conscientiousness or extroversion.

Conclusion

IBS patients with a higher level of neuroticism were more likely to experience higher levels of GI-specific and general anxiety. The trait neuroticism and/or agreeableness was more likely to have a significant lower mental quality of life in IBS. These findings emphasize the contribution of personality traits in the pathophysiology and course of IBS, pleading for a more personalized approach in patient management.

Introduction

Irritable bowel syndrome (IBS) is a chronic gut-brain disorder that can be responsabil for a variety of uncomfortable gastrointestinal symptoms (laid out in the Rome Criteria) that can reduce quality of life. Although the precise mechanism remains unknown, recent research suggests that an imbalance in intestinal microbiota and a dysfunctional gut-brain axis may be involved in the development of IBS. Because of this, methods to restore the microbiota have been explored as treatment for this condition.

Aims & Methods

Randomized placebo controlled trial 180 patients: active group (probiotic formula, 3g/day- 92, placebo group – 88. men and women aged 24 to 75 who met the Rome IV criteria. One sachet probiotic (3 g) contains 7.5 billion bacteria: Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, Bifidobacterium lactis W52, Lactobacillus paracasei W20 Lactobacillus plantarum W62, Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus salivarius W24. Assessments were made at 4, 8, 12 weeks. All patients agreed to maintain their lifestyle behaviors during their participation in the study. Exclusion criteria: chronic gastrointestinal condition (other than IBS), including inflammatory bowel disease, lactose intolerance, celiac disease, diabetes, neoplasms.Patients have complete weekly data on stool frequency and consistency (Boston scale) and intensity of IBS symptoms (abdominal pain/discomfort, bloating, flatulence/borborygmi, and difficulty defecating) on a Likert scale of 0 (absent) to 7 (severe). Participants completed an IBS-specific quality of life questionnaire (IBS-QoL) at randomization (V1), fallow-up (V2) and at the end of the intervention (V3). Primary endpoint was mean weekly scores of gastrointestinal symptoms. Responders of abdominal pain were defined as subjects who experienced a reduction of at least 30% of the mean daily abdominal score reported at baseline (week 0). Secondary endpoints were the total AUC (W0-W12) of abdominal symptoms (abdominal pain, bloating and flatulence/borborygmi).

Results

​There is a significant reduction in abdominal pain and bloating scores trough all 12 weeks of supplementation versus placebo. A higher overall IBS-QOL score, indicative of better QOL was reported at the end of the intervention (specially for interference with activity P=0.05, body image P=0.040, food avoidance P=0.03)

Conclusion

​The probiotic treatment provides statistically significant and clinically relevant benefits for individuals with IBS. Improves gastrointestinal symptoms and quality of life in IBS patient

References

Rome IV criteria-Rome Foundation

Introduction

The integrity of the intestinal barrier is crucial in preventing bacterial translocation and systemic inflammation, both of which contribute to the progression of advanced chronic liver disease (ACLD). While surrogate biomarkers exist, direct real-time assessment of intestinal barrier function has been challenging. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that allows direct visualization of mucosal integrity during endoscopy.

Aims & Methods

The present study aims to determine the prevalence of CLE-detectable barrier dysfunction in ACLD patients, to explore its association with disease severity, and to assess its prognostic significance. In our prospective study, 48 ACLD patients who underwent routine upper gastrointestinal endoscopy between 11/2022 and 04/2024 were examined using CLE (Cellvizio®) in the duodenum following intravenous fluorescein injection (2.5–5 mg). The presence or absence of fluorescein leakage into the intestinal lumen was determined. The presence of leakage in more than three different locations in the duodenum was indicative of intestinal barrier dysfunction. Clinical data including Child-Turcotte-Pugh (CTP) score, MELD score, hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and biomarkers of liver function were recorded. Patients were followed for a median of 13.2 months, with liver-related events (LRE) including first or further decompensation, acute-on-chronic liver failure (ACLF), and liver-related death as endpoints.

Results

Intestinal barrier dysfunction was detected in 52% of patients and was found to be significantly more prevalent in decompensated ACLD compared to compensated ACLD (73% vs. 25%, p=0.021). CLE-based barrier dysfunction correlated with bilirubin (p=0.033) and albumin (p=0.010), but not with HVPG (p=0.314), LSM (p=0.482), or C-reactive protein (p=0.457). Patients exhibiting intestinal barrier dysfunction demonstrated a significantly higher risk of LRE during follow-up (25% vs. 5% at 12 months, 43% vs. 5% at 18 months, log-rank p=0.005). In univariable Cox regression analysis, intestinal barrier dysfunction remained independently associated with LRE (hazard ratio: 2.36, 95% confidence interval: 1.34–84.0, p=0.025). Importantly, the prognostic impact of CLE findings aligned with established risk markers such as MELD and albumin.

Conclusion

CLE provides real-time, high-resolution insight into intestinal barrier integrity in ACLD patients. The strong correlation between CLE-detected barrier dysfunction and adverse clinical outcomes suggests that CLE has the potential to serve as a prognostic instrument for risk stratification. As CLE can be integrated into standard endoscopic procedures, it may provide an accessible and clinically relevant means of assessing intestinal barrier function in routine practice in patients with liver cirrhosis. Further studies in larger cohorts are needed to validate CLE for routine clinical use and to explore therapeutic interventions targeting intestinal barrier dysfunction.

Disclosure

NO CoI to declare

Introduction

Lynch syndrome (LS) is associated with an increased risk of upper gastrointestinal (GI) cancers. While upper GI surveillance is recommended in several guidelines, there remains international variability and ongoing debate regarding its implementation, timing, and extent. This study evaluated the incidence of gastric (GC), duodenal (DC), and jejunal cancers (JC) in LS patients using data from the German Consortium for Familial Intestinal Cancer (GCFIC). In addition, the diagnostic yield of esophagogastroduodenoscopy (EGD) and push enteroscopy (PE), performed at a tertiary care center, was retrospectively analyzed.

Aims & Methods

A total of 960 endoscopic procedures (494 EGD, 466 PE) were retrospectively analyzed in 349 LS patients documented at a tertiary care center. Push enteroscopy (PE) was performed using a colonoscope to allow deeper insertion into the small intestine, enabling inspection of the proximal jejunum. Clinically relevant findings included intestinal metaplasia, Barrett’s esophagus, adenomas, and carcinomas. These findings were systematically compared between EGD and PE to evaluate diagnostic yield. The GCFIC database was evaluated to determine cancer incidence by genotype.

Results

In the GCFIC cohort (n=2859), the majority of GC (2.2%), DC (2.1%), and JC (1.9%) occurred in high-risk pathogenic variant carriers (PGV) (MLH1, MSH2, EPCAM). However, a small proportion of cancers was also observed in low-risk PGV carriers: GC in two MSH6 carriers, DC in five patients with MSH6 or PMS2, and JC in seven low-risk carriers (MSH6: 3, PMS2: 4). In the NZET cohort, 22% of procedures and 50 % of patients revealed relevant findings. Gastric adenomas were found in 3.7%, gastric cancer in 1.1%, and intestinal metaplasia in 28% of patients. Duodenal adenomas were found in 3.7% and cancer in 0.9%. Jejunal neoplasia was detected exclusively by PE (adenomas 1.7%, cancer 0.6%).

Conclusion

Upper gastrointestinal surveillance is essential in patients with Lynch syndrome. Push enteroscopy (PE) provides diagnostic value beyond conventional esophagogastroduodenoscopy (EGD), particularly in detecting jejunal neoplasia, and should be considered in high-risk surveillance protocols.

Disclosure

Robert Hüneburg was funded by Deutsche Krebshilfe (DECADE), and Wilhelm-Sander-Stiftung.
Jacob Nattermann was funded by Wilhelm-Sander-Stiftung.