Introduction

Somatization is defined as a tendency to experience and communicate psychological distress in the form of somatic symptoms. Literature suggests that there is a link between somatization and irritable bowel syndrome (IBS). Nevertheless, the association between clinical symptoms of IBS and somatization, especially in children, remains unclear.

Aims & Methods

54 children aged 6-12 with a verified diagnosis of IBS according to Rome criteria IV were included in the study. The control group consisted of 50 healthy children of the same age and gender. The level of somatization was assessed by the Somatoform Symptom Screening test (SOMS-2J by Rief, W., & Hiller, W.), which was modified for children. The intensity of abdominal pain and dyspeptic symptoms were estimated using a 4-point Likert scale. Data were processed using Microsoft Excel 2016 and analyzed with GraphPad (Prism 5.0). Pearson test was used to assess the correlation between SOMS rate and the intensity of somatic complaints.

Results

The level of somatization was significantly higher in children with IBS in comparison to the control group (p<0.0001). There was no difference in somatization rate in patients according to the predominant bowel habit. A direct correlation between the intensity of abdominal pain and the level of somatization (r=+0.37; p=0.005) was established in children with IBS (Fig.1). On the contrary, the intensity of dyspeptic symptoms was less influenced by the rate of somatization (r=+0,18; p=0,20).

Conclusion

To conclude, children with IBS who had higher rates of somatization were revealed to have a higher intensity of somatic complaints, especially abdominal pain. We suggest that somatization plays an important role in the occurrence of somatic symptoms of IBS. It may be one of the reasons for the low effectiveness of pharmacological treatment of IBS in children.

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

While the mechanistic background to functional bowel disorders, including irritable bowel syndrome (IBS) is insufficiently understood, there is growing evidence that cytokine imbalance and inflammation may contribute to IBS pathogenesis.

Aims & Methods

We undertook a comprehensive investigation of serum cytokine profiles in individuals with functional bowel disorders (IBS n=164, functional constipation n=6, functional diarrhea n=3) and healthy controls (n=31), mapping their associations with clinical symptoms (GSRS-IBS, HAD), the gut microbiome (whole-metagenome sequencing of fecal samples), colonic mucosal responses (bulk RNA sequencing of sigmoid biopsies), intestinal physiological parameters, and the serum metabolome (liquid chromatography-mass spectrometry). Serum levels of IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IL-17A and CXCL10 were measured with Meso Scale Discovery (MSD) multiplex immunoassay kits.

Results

While cytokine levels did not differ significantly between persons with functional bowel disorders and healthy individuals, CXCL10 was reduced in participants with predominant diarrhea (IBS-D and functional diarrhea, p=0.01), whereas IL-12p70 was increased in predominant constipation (IBS-C and functional constipation, p=0.03), compared to healthy controls. Within both the full study cohort and participants with functional bowel disorders, IL-12p70 levels correlated with oroanal transit time (rho 0.20 and 0.19, p=0.007 and 0.01, respectively), and were inversely associated with fecal short-chain fatty acids (p=0.006, 0.01 and 0.03 for acetate, propionate and butyrate, respectively), as well as with the abundance of several butyrate-producing species. By contrast, IL-12p70 levels were positively associated with mucus-resident species (e.g., from the Akkermansia and Victivallis genera), with metabolites potentially derived from the degradation of mucosal carbohydrates, and with a distinct T helper 1 type response in colonic biopsies. Moreover, IL-12p70 levels correlated with anxiety (rho 0.17, p=0.03) in participants with functional bowel disorders.

Conclusion

Systemic cytokine profiles did not discriminate persons with functional bowel disorders from healthy individuals, but participants with predominant constipation and diarrhea exhibited distinct cytokine profiles. Alteration of systemic cytokines, notably IL-12p70, may result from disrupted mucosal barrier integrity and host-microbe homeostasis, and contribute to extraintestinal symptoms in a subset of individuals with functional bowel disorders.

Introduction

Studies have shown that adults with irritable bowel syndrome (IBS) may be associated with anxiety, mood disorders, chronic headache, and other neuropsychiatric conditions. This growing body of evidence can allude to a possible bidirectional gut-brain connection. While adolescence is the age when both IBS and neuropsychiatric illnesses often first manifest, this population remains under-studied.

Aims & Methods

We aim to assess the association between the presence of irritable bowel syndrome (IBS) and neurologic and psychiatric disorders in a nationwide cohort of adolescents. This cross-sectional study included all adolescents aged 16-21 who underwent mandatory medical evaluations as part of their conscription between 2000-2021. All individuals completed comprehensive medical interviews. Suspected diagnoses prompted referral to board-certified specialists for confirmation and severity grading based on predefined criteria. IBS was diagnosed according to the Rome II-IV criteria by a certified gastroenterologist.
Neurologic disorders included attention-deficit/hyperactivity disorder [ADHD], epilepsy, chronic headache, sleep disorders. Psychiatric disorders included psychotic, personality, general anxiety disorder [GAD], non-combat post-traumatic stress disorder [PTSD], mood, dissociative, and eating disorders. Each diagnosis was classified by severity (mild, moderate, severe). Unadjusted and multivariate-adjusted logistic regression models were fitted to estimate odds ratios (ORs) for associations with IBS. The adjusted models were accounted for age, sex, intelligence score, body mass index (BMI), socioeconomic status (SES), education, country of origin, and any concurrent neuropsychiatric diagnoses.

Results

The study included 1,561,717 adolescents (666,442 [42%] women, mean age 17.4 ± 1.4 years), of whom 7,230 (0.46%) were diagnosed with IBS (4,778 mild; 1,948 moderate; 504 severe). Neurologic disorders were present in 1,661 (23.0%) and 143,348 (9.2%) of those with and without IBS, respectively. The respective numbers of people with psychiatric disorders were 773 (10.7%) and 49,889 (3.2%). In multivariable adjusted models, those with IBS were more likely to have chronic headache (aOR 4.7, 95% CI: 4.4-5.1), GAD (aOR 3.6, 95% CI: 3.2-3.9), eating disorders (aOR 2.6, 95% CI: 1.9-3.5), mood disorders (aOR 2.5, 95% CI: 2.1-3.1), personality disorders (aOR 2.5, 95% CI: 2.1-2.9), and dissociative disorders (aOR 19.1, 95% CI: 12.5-28.9). Patients with severe IBS (n=504) were independently associated with the presence of at least one severe neurologic (aOR 2.9, 95% CI: 1.2-7.1) or psychiatric disorder (aOR 3.8, 95% CI: 2.6-5.4).

Conclusion

In this large nationwide cohort, adolescents with IBS were more likely to have several tested neurologic and psychiatric disorders, compared to those without IBS. Longitudinal studies are needed to explore the directionality and long-term implications of these associations.