Clinical Case Summary

A 57 years-old patient with a history of active smoking, moderate body overweight (BMI 29 Kg/mq) and mild systolic hypertension in treatment with Olmesartan complained history of chronic diarrea and abdominal pain since 2006, rarely associated with hematochezia. After replacement of antihypertensive therapy to eliminate a potential confouding factor, he underwent multiple colonoscopies through the years with nonspecific findings until 2017, when moderated discontinuos inflammation with multiple erosions was seen in the transverse colon and in the rectum. Histologic examination described presence of chronic inflammation with cryptic microabscesses and cryptitis suggetive for Crohn's disease, while intestinal ultrasound revealed no small bowel localizations. He was treated with 2.4 daily grams of oral mesalamine with benefit until the end of 2023, when he came up to our clinic complaining resumption of bloody diarrhoea and abdominal pain, with 3-4 liquid stools per day. Addition of topic mesalamine was not of benefit. The patient underwent another colonoscopy which confirmed presence of hyperemic mucosa with diffuse erosions in the rectum, with histology confirming active Inflammatory Bowel Disease. In march 2024, after neurological investigations for recurrent paresthesias and strength deficits, the patient was diagnosed with relapsing-remitting Multiple Sclerosis. After multidisciplinary consultation, negative cardiologic evaluation, chest X-ray and blood screening exams, in October 2024 the patient started the anti sphingosine-1 phosphate Ozanimod, which was well-tolerated at maintenance dose of 0.92 milligrams per day. Three months after, he came back for scheduled follow-up reporting 1 or 2 daily evacuations in absence of abdominal pain and rectal bleeding. Calprotectin levels droped up to 17 ug/g. He also described complete neurological remission and complete absence of drug side effects.

References

1) Feagan BG, Schreiber S, Afzali A, Rieder F, Hyams J, Kollengode K, Pearlman J, Son V, Marta C, Wolf DC, D'Haens GG. Ozanimod as a novel oral small molecule therapy for the treatment of Crohn's disease: The YELLOWSTONE clinical trial program. Contemp Clin Trials. 2022 Nov;122:106958.
2) Pérez-Jeldres T, Alvarez-Lobos M, Rivera-Nieves J. Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis. Drugs. 2021 Jun;81(9):985-1002. Erratum in: Drugs. 2021 Aug;81(12):1451.
3) Harris S, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Yan J, Wu C, Hu Y, Maddux R, Wolf DC, D'Haens G. Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease. Dig Dis Sci. 2024 Jun;69(6):2044-2054.
4) Sands BE. Positioning Sphingosine-1 Phosphate Receptor Modulators in Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y). 2024 Jul;20(7):417-420.
5) Cree BA, Selmaj KW, Steinman L, Comi G, Bar-Or A, Arnold DL, Hartung HP, Montalbán X, Havrdová EK, Sheffield JK, Minton N, Cheng CY, Silva D, Kappos L, Cohen JA. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial. Mult Scler. 2022 Oct;28(12):1944-1962. doi: 10.1177/13524585221102584. Epub 2022 Jun 28. Erratum in: Mult Scler. 2022.

Introduction

Non-invasive biomarkers that enable accurate diagnosis, patient stratification, and therapy monitoring in irritable bowel syndrome (IBS) are still lacking in clinical practice. Volatile organic compounds (VOCs) produced by the host metabolism, inflammatory processes, and the gut microbiota are present in exhaled breath and have recently gained attention as promising biomarker candidates. Prior research (Van Malderen et al. (2020)) demonstrated that breath VOC profiling could accurately distinguish IBS patients from healthy controls using multicapillary column/ion‑mobility spectrometry (MCC/IMS).

Aims & Methods

The present study aimed to assess the potential of high-resolution gas chromatography-quadrupole time‑of‑flight mass spectrometry (GC-QTOF-MS) profiling of breath VOCs to define distinct compound classes that enhance the mechanistic understanding of breath-based biomarkers in IBS. To this end, breath samples from 12 IBS patients and 11 healthy controls were collected, together with matched ambient air samples and were analyzed using GC-QTOF-MS. Breath samples were corrected by background subtraction and least‑absolute‑shrinkage‑and‑selection‑operator (LASSO) regression was applied with leave‑one‑out cross‑validation (LOOCV) to identify discriminative VOC signatures. The feature set was subsequently filtered to exclude sporadically detected VOCs and compounds of exogenous (non-host) origin. Finally, the remaining VOCs were mapped to putative pathways.

Results

IBS patients had a mean ± SD age of 36 ± 15.3 years, compared with 56 ± 15.4 for the healthy controls. The male-to-female ratio was 3:9 in the IBS cohort and 5:6 among the healthy controls. Within the IBS group, 7 patients had diarrhea-predominant IBS, 4 had constipation-predominant IBS, and 1 had mixed-type IBS. The LASSO regression model, validated with LOOCV, demonstrated high discriminative performance in differentiating IBS patients from healthy controls, with the corresponding model metrics in Table 1. Furthermore, the feature selection identified a panel of discriminative VOCs - predominantly alkanes, aldehydes, and ketones - that were up-regulated in the IBS breath profiles. These elevated compound classes could putatively be linked to mechanisms relevant to IBS pathophysiology, including altered microbial metabolism, increased oxidative stress, and low-grade inflammation.

Table 1: Model metrics

Conclusion

Volatomic breath profiling in IBS, shows great potential for discriminating IBS from healthy controls and for defining clinically relevant biomarkers composed of specific VOCs. Nonetheless, the limited sample size might risk model overfitting and introduces uncertainty in the estimates. Further research including larger, confounder-controlled cohorts is necessary, along with the targeted validation of the identified VOCs to further confirm their mechanistic role in IBS.

References

Van Malderen K, Hanning N, Lambrechts H, Haverhals T, Van Marcke S, Ceuleers H, De Man JG, De Winter BY, Lamote K, De Schepper HU. Volatile organic compound profiling as a potential biomarker in irritable bowel syndrome: A feasibility study. Front Med (Lausanne). 2022 Aug 4;9:960000. doi: 10.3389/fmed.2022.960000. PMID: 35991639; PMCID: PMC9388331.

Introduction

Endoscopic submucosal dissection (ESD) is being increasingly adopted worldwide for the treatment of colorectal neoplastic lesions. However, its role in patients with inflammatory bowel disease (IBD) remains debatable, particularly due to the increased risk of submucosal fibrosis from chronic inflammation, which can theoretically impact the clinical outcomes of this technique. This study aimed to assess the efficacy and safety of ESD for colorectal neoplastic lesions in IBD patients, comparing Asian and Western settings.

Aims & Methods

A systematic review was conducted by searching MEDLINE and Web of Science until January 2025, in accordance to MOOSE guidelines. We included primary studies reporting ESD performance in IBD patients. We performed random-effects meta-analysis for several outcomes, including en-bloc, R0, and curative resection rates, frequency of adverse events (post-procedural bleeding and perforation), local recurrence and need for additional surgery after ESD. Certainty of evidence was assessed using GRADE.

Results

We included 20 studies (565 patients and 732 lesions). The meta-analytical frequencies of en-bloc, R0, and curative resection rates were 95.7% (95%CI=93.5-97.9%; I²=60.1%), 84.6% (95%CI=79.4-90.1%; I²=68.9%), and 83.9% (95%CI=76.3-92.4%; I²=75.9%), respectively. Bleeding and perforation occurred in 7.0% (95%CI=4.4-11.2%; I²=16.9%) and 7.9% (95%CI=5.3-11.9%; I²=2.4%) of cases, respectively. Local recurrence frequency was 5.3% (95%CI=3.5-7.9%; I²=0%). The meta-analytical need for additional surgery was 13.3% (95%CI=9.5-18.1%; I²=42.5%). No differences were found between Asian and Western studies for any outcome. The certainty of evidence was considered "low" in 4 outcomes and "very low" in the remaining outcomes.

Conclusion

ESD appears feasible and safe for treating IBD-associated colorectal neoplasias. Similar results were observed between Asian and Western studies.

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.

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 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