Introduction

Growing evidence supports the role of environmental factors, such as diet and lifestyle, in modulating the intestinal microbiota and potentially influencing the symptoms of chronic gastrointestinal disorders. This study aimed to correlate lifestyle habits with colonic microbiota composition in patients with Inflammatory Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS), compared to healthy controls (HCs).

Aims & Methods

38 IBD, 44 IBS and 48 HC were recruited. Fecal microbiota composition was analyzed by sequencing the 16S rDNA V3/V4 region using the Illumina platform. Dietary habits and physical activity levels were assessed using a 7-day food diary, a Food Frequency Questionnaire, and the IPAQ. Urinary indican was measured via colorimetric assay and HPLC, fecal zonulin levels were assessed using ELISA, and selected circulating microRNAs were analyzed in plasma and serum by TaqMan-based quantitative Real-Time PCR.

Results

A significant reduction in dietary fiber intake was observed in both IBD and IBS patients compared to healthy controls (HCs) (p < 0.05). IBS patients engaged in more moderate physical activity than HCs (p < 0.05). Reduced fiber intake was associated with decreased microbial diversity (p < 0.005), compared to adequate fiber consumption. Microbiota analysis revealed a reduction in alpha diversity in IBD patients compared to HCs, particularly in terms of phylogenetic diversity and observed features, while IBS patients showed intermediate values. Beta diversity (weighted and unweighted UniFrac) demonstrated a clear separation among the three groups, with the most pronounced differences observed between IBD and the other conditions. LEfSe analysis identified the highest number of discriminant taxa in HCs, consistent with their greater microbial biodiversity. No clearly pathogenic organisms were identified in either IBD or IBS patients, suggesting that the observed alterations may result from a loss of beneficial commensals rather than the presence of harmful species. Additionally, greater microbial diversity was found in individuals living in rural areas compared to those in urban environments. IBD and IBS patients not adhering to the Mediterranean Diet (MD) showed significantly higher zonulin levels than those following the MD (p < 0.001 and p = 0.003, respectively). Finally, miRNAs involved in inflammatory and epithelial permeability pathways were differentially expressed in both IBD and IBS patients. MiR-24 was significantly dysregulated in IBD (p = 0.01), while miR-923 also showed a significant difference in the same group (p = 0.05). MiR-221 exhibited a non-significant trend toward upregulation in IBS. These findings suggest a potential role for these miRNAs in the molecular mechanisms underlying inflammatory and functional bowel disorders.

Conclusion

The preliminary results of the present study underlined the impact of lifestyle factors, particularly diet and physical activity, on intestinal microbiota composition and barrier function in IBD and IBS. Microbial and molecular markers may support a more personalized approach to these disorders.

References

1. Alfaifi, J. et al; Deep Dive Into MicroRNAs in Inflammatory Bowel Disease. Inflamm. Bowel. Dis. 2023
2. Cena, H. et al; Biodiversity and planetary health: A call for integrated action. Lancet 2024
3. Giammona A et Al: Chronic Gastrointestinal Disorders and miRNA-Associated Disease: An Up-to-Date. Int J Mol Sci 2025
4. Ventham, N.T.et al.; Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease. Nat. Commun. 2016

Introduction

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract often complicated by intestinal strictures. Accurate differentiation between inflammatory and fibrotic strictures is essential for guiding therapeutic strategies but remains challenging with current diagnostic tools. The capability of greyscale intestinal ultrasound (IUS) alone for characterizing inflammation versus fibrosis in CD strictures is not accurate enough to be used in clinical practice. This study investigates the diagnostic utility of advanced ultrasound techniques, including shear wave elastography (SWE), MV-Flow Doppler, and the Limberg score (LS), in the evaluation of strictures in patients with CD.

Aims & Methods

A prospective cross-sectional study enrolled 15 consecutive patients with ileal and ileocolonic CD scheduled for surgery due to symptomatic strictures. Each patient underwent intestinal ultrasound, including SWE, MV-Flow Doppler imaging, and LS assessment of the stenotic segment, within one week before surgery. Histopathological analysis of resected bowel specimens was then performed to grade inflammation and fibrosis according to a semiquantitative scoring system. Statistical analysis evaluated the correlation between ultrasound parameters and histological findings.

Results

SWE reliably differentiated fibrotic grades, with mean stiffness values significantly increasing from mild to severe fibrosis (P = 0.014). A cutoff of 24.85 kPa distinguished mild from moderate/severe fibrosis with 83.33% sensitivity and 88.89% specificity (AUC = 0.944). Conversely, SWE did not significantly distinguish between grades of inflammation (P = 0.643). MV-Flow Doppler values strongly correlated with histological inflammation grades (P = 0.007), with mean microvascular percentages increasing from 8.1% (mild inflammation) to 36.2% (severe inflammation). The LS also demonstrated high diagnostic accuracy for severe inflammation (AUC = 0.910, sensitivity 80.0%, specificity 90.0%).

Conclusion

This study underscores the complementary roles of SWE, MV-Flow, and LS in characterizing strictures in CD. SWE excels in assessing fibrosis, while MV-Flow and LS provide sensitive measures of inflammation. The integration of these modalities with conventional greyscale IUS offers a comprehensive and non-invasive approach to optimize diagnosis and management of CD strictures. Future research should validate these findings in larger, multicenter studies and explore their longitudinal applications.

Introduction

Active ulcerative colitis (UC) is typically assessed through clinical manifestations, laboratory examinations, and colonoscopy, which also determine the disease's severity.
An easy-to-use and patient-friendly technique for early clinical suspicion confirmation is intestinal ultrasonography (IUS). Ancillary technologies such as elastographic techniques have recently become available and can be used in conjunction with traditional IUS.

Aims & Methods

The study aim was to assess the accuracy and reproducibility of intestinal 2D-shear Wave Elastography (2D-SWE) as a predictor of disease’s activity and mucosal healing (MH). 2D-SWE was performed in 34 consecutive patients with active disease confirmed by colonoscopy. The 2D-SWE measurements (n. 10 with IQR/Med < 30%) was taken in the sigmoid colon by two independent operators at basal and 3 months after the starting of a new treatment regimen. The correlation between 2D-SWE and the Mayo endoscopic score (MES) was investigated along with clinical and conventional ultrasound parameters such as Bowel Wall Thickness (BWT) and Limberg score (LS).

Results

2D-SWE values (kPa) positively correlated with MES with a statistically significant difference between mucosal healing (MH) and active disease groups (p = 0.003). The AUROC (95% CI) for assessing mucosal healing by 2D-SWE was 0.84 (95% CI: 0.70-0.97). Using a cut off value of 21.5 kPa, sensibility and the specificity for mucosal healing were 0.62 and 0.99, respectively. The median 2D-SWE values obtained by the two independent operators were 19.7 kPa (IQR 16.2-26.8) and 17.7 kPa (IQR 14.4-23.7) respectively. 2D-SWE was also positively correlated with rectal bleeding, LS and BWT (r 0.38 p=0.027; r 0.43 p=0.014; r 0.33 p=0.057) but not with fecal calprotectin and C-reactive protein. No significant correlation was found between 2D-SWE values and clinical remission (Partial Mayo Score ≤ 2) after 3 months of a new treatment regimen (p = 0.491).

Conclusion

This study demonstrated the feasibility of 2D-SWE technique with an excellent inter-observer repeatability. The technique showed good accuracy in predicting mucosal healing, with increasing values correlating with disease severity. In the future, 2D-SWE could help reduce the number of colonoscopies and improve clinical decision making.

Disclosure

No discosure to declare

Introduction

Inflammatory bowel disease (IBD) is associated with an increased risk of cerebrovascular disease (CVD) and coronary heart disease (CHD). It has been suggested that chronic inflammation may be the mechanism. Previous studies have primarily assessed IBD as a group and not ulcerative colitis (UC) or Crohn’s disease (CD) separately.

Aims & Methods

This study aims to determine the relationship between UC and CD and CVD and CHD risk factors/outcomes in a large UK population. General practice electronic medical records were sourced from the United Kingdom (UK) via The Health Improvement Network (THIN). UC and CD risk factors and disease outcomes were identified through Read codes.

Results

Factors	UC Prevalence, n (%) n=3,432	UC Odds Ratio, 95% CI	CD Prevalence, n (%) n=2,831	CD Odds Ratio, 95% CI
Female Sex	1,796 (52.3%)	1.16, 1.09-1.25	1,689 (59.7%)	2.71, 2.08-3.62
Age	43.95 ± 14.4	0.99, 0.99-0.99	45.7 ± 15.7	0.95, 0.94-0.96
Diabetes Type II	417 (12.2%)	1.50, 1.35-1.66	265 (9.4%)	1.12, 0.98-1.27
Dyslipidemia	176 (5.1%)	1.26, 1.08-1.47	112 (4.0%)	0.96, 0.79-1.16
Obesity	7 (0.2%)	0.99, 0.47-2.10	7 (0.3%)	1.21, 0.58-2.55
AMI	113 (3.3%)	1.57, 1.30-1.89	57 (2.0%)	0.95, 0.73-1.23
Ischemic Stroke	47 (1.4%)	1.46, 1.09-1.95	23 (0.8%)	0.86, 0.57-1.30
Intracranial Hemorrhage	15 (0.4%)	1.67, 1.01-2.78	10 (0.4%)	1.35, 0.72-2.51
COPD	31 (0.9%)	1.85, 1.30-2.64	24 (0.9%)	1.74, 1.16-2.59

A total of 1,062,022 unique adult patients were available for analysis. There were 3,432 UC (mean age: 43.95 years, SD=14.4 years; 52% female) and 2,831 CD cases (mean age: 40.9 years, SD=14.06 years; 60% female).

Ulcerative Colitis: Univariate analysis in Table 1. Multiple logistic regression (MLR) of CHD risk factors and outcomes (adjusted in all models for age, sex, diabetes, COPD, dyslipidaemia, obesity, and statins) revealed statistically significant independent CHD risk factors: female sex (OR: 1.19, 95%CI: 1.11-1.28), younger age (OR: 0.98, 95%CI: 0.98-0.99), type 2 diabetes (OR: 1.22, 95%CI: 1.09-1.37), and increased risk of acute myocardial infarction (AMI) (OR: 1.35, 95%CI: 1.11-1.64).
MLR of CVD risk factors and outcomes (adjusted as above plus thrombolytic agents) found statistically significant independent CVD risk factors: female sex (OR: 1.19, 95%CI: 1.10-1.27), younger age (OR: 0.99, 95%CI: 0.98-0.99), diabetes type 2 (OR: 1.20, 95%CI: 1.07-1.34), statin use (OR: 1.13, 95%CI: 1.03-1.25), and any anti-thrombolytic agents (OR: 1.37, 95%CI: 1.25-1.51).
Crohn’s Disease: Univariate analysis in Table 1. MLR of CHD risk factors and outcomes (adjusted) revealed statistically significant independent CHD risk factors: female sex (OR: 0.92, 95%CI: 0.85-0.99), younger age (OR: 0.98, 95%CI: 0.97-0.99), statin use (OR: 1.23, 95%CI: 1.11-1.36), and an increased likelihood of death (OR: 1.28, 95%CI: 1.12-1.47).
MLR of CVD risk factors and outcomes (adjusted) revealed statistically significant independent CVD risk factors: female sex (OR: 0.91, 95%CI: 0.84-0.98), younger age (OR: 0.97, 95%CI: 0.96-0.98), anti-thrombolytic agents (OR: 1.71, 95%CI: 1.55-1.90), and an increased likelihood of death (OR: 1.18, 95%CI: 1.03-1.35).

Conclusion

UC cases are more likely to be female, have diabetes, be taking statins, and anti-thrombolytic agents, and have an increased risk of AMI and death. CD cases are less likely to be female, but more likely to be taking statins, anti-thrombolytic agents, and more likely to die.

Disclosure

Guy D. Eslick and Michael P. Jones have nothing to disclose. Nicholas J. Talley Disclosures: GutSee Ltd (consulting microbiome, 2025), Brown University, Agency for Health Care Research and Quality (fiber and laxation) (2024), Rome Foundation (member gastroduodenal committee) (present) Biocodex (FD diagnostic tool) (present) Microba (consulting microbiome - commencing 2025) Comvita Manuka Honey (FD trial consulting) (2025), BluMaiden outside the submitted work. In addition, Dr. Talley has a patent Nepean Dyspepsia Index (NDI) 1998, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, ”Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Patent Application No. 63/537,725.
Boards: The Gut Foundation Board (2025-present), Asia Pacific Association of Medical Editors (APAME) Board (President 2023-2025), Doctors for the Environment (Chair 2024-present), Luminal Faculty GESA (Chair) (2023-2025)
Editorial: UptoDate (Section Editor), Mayo Clinic Proceeding Associate Editor (2023-present)
Financial support: Dr. Talley is supported by funding from the National Health and Medical Research Council (NHMRC) to the Centre for Research Excellence in Digestive Health and he holds an NHMRC Investigator grant.

Clinical Case Summary

A 24-year-old male presented with jaundice and mild vertigo after a 10-day prodrome (asthenia, nausea, headache, fever). Ibuprofen (1200 mg/d) was taken for these symptoms only during the first 5 days. Labs revealed acute hepatocellular injury and elevated cholestasis (AST 215, ALT 862, FA 134, GGT 126 IU/L), marked mixed hyperbilirubinemia (Total 13.5 mg/dL, Direct 7.58 mg/dL) and coagulopathy (INR 1.59). Ultrasound showed hepatosplenomegaly. Viral hepatitis (HAV/HBV/HCV/CMV) and autoimmune/metabolic causes were excluded. Epstein-Barr Virus (EBV) serology showed low-titer positive VCA IgM but negative VCA IgG, EBNA IgG, and serum EBV DNA PCR, indicating recent non-active infection. Given ibuprofen timing and high RUCAM score, drug-induced liver injury (DILI) with a hepatocellular pattern was suspected. Liver biopsy confirmed acute hepatitis with lymphomonocytic infiltrate, necrosis and canalicular cholestasis. Despite improving liver function tests post-ibuprofen cessation, he developed worsening vertigo, severe ataxia, nausea, vomiting, hypophonia, necessitating nasogastric feeding/bed confinement. Cerebrospinal fluid (CSF) showed mild mononuclear pleocytosis (16 cells/mm³); a multiplex PCR pathogen panel (including EBV) was negative. Brain MRI/EEG were normal. Post-infectious EBV acute cerebellar ataxia was diagnosed concurrently with DILI, based on timing post-recent EBV, exclusion of active neurological infection (negative CSF PCR, normal imaging), mild pleocytosis, and supported by later IgG seroconversion. IV methylprednisolone treatment, chosen for clinical severity, led to significant neurological improvement within days and eventual recovery after physiotherapy. This case highlights the significant challenges of diagnosis and management of concomitant DILI and recent EBV infection with neurological sequelae, requiring careful differentiation of liver damage patterns (hepatocellular DILI vs cholestatic EBV) and optimal management of neurological symptoms.

References

Illustrative Material References:
- Liver biopsy histology slides (highlighting lymphomonocytic infiltrate, necrosis, and canalicular cholestasis characteristic of DILI).
- Table/Graph showing serial Liver Function Tests (AST, ALT, Bilirubin) over time, depicting injury peak and recovery trend.
- Table summarizing sequential Epstein-Barr Virus (EBV) serology results (VCA IgM, VCA IgG, EBNA IgG) demonstrating seroconversion.
- Table summarizing Cerebrospinal fluid (CSF) analysis results (cell count, protein, glucose, negative multiplex PCR).
- Representative Brain MRI images (axial/sagittal views) confirming absence of structural lesions or encephalitis signs.

Introduction

Among immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs), gastrointestinal irAEs (GI-irAEs) are relatively rare, and their risk factors and prognostic implications remain unclear.

Aims & Methods

We retrospectively analyzed 1,104 patients who initiated ICI therapy at our institution between January 2016 and December 2022 and for whom survival data were available. GI-irAEs were defined as colitis with an increase of ≥3 bowel movements/day from baseline in the absence of other causes, or symptomatic gastritis confirmed histologically. Risk factors and prognostic impact of GI-irAEs were evaluated.

Results

The median duration of ICI therapy was 107 days. The cohort included 754 males (68%) with a median age of 69 years. The primary tumor types were lung cancer (32%), gastrointestinal cancers (19%), urothelial carcinoma (13%), head and neck cancer (13%), and melanoma (11%). The overall response rate was 27.8%, and the disease control rate was 49.0%. irAEs of any grade occurred in 310 patients (28%), and GI-irAEs were observed in 30 patients (2.7%). In univariate logistic regression analysis, use of anti-CTLA-4 antibody, combination ICI therapy, a prognostic nutritional index (PNI) ≥ 40, and platelet-to-lymphocyte ratio (PLR) ≥ 1.8 were associated with an increased risk of GI-irAEs. In multivariate analysis, only anti-CTLA-4 antibody use remained a significant risk factor (odds ratio: 9.2; 95% CI: 1.9–45). Kaplan–Meier analysis revealed that patients with GI-irAEs had significantly longer overall survival (OS) compared to those without irAEs in the overall cohort (median OS: 22.9 vs. 12.6 months, P < 0.0001). However, this difference was not observed in landmark analyses at 4 and 8 weeks post-treatment. Subgroup analysis based on PNI showed that in patients with PNI ≥ 40, those with GI-irAEs had significantly longer OS than those without irAEs (median not reached vs. 19.3 months, P = 0.0003). In contrast, in patients with PNI < 40, GI-irAE cases tended to have shorter OS than non-irAE cases (8.2 vs. 9.3 months). This trend was consistent in landmark analyses at 4 and 8 weeks.

Conclusion

The impact of GI-irAEs on prognosis appears to differ depending on the patient’s nutritional status. Particular caution is warranted for patients in poor general condition receiving ICIs, especially those involving anti-CTLA-4 antibodies, as GI-irAEs may serve as a poor prognostic factor in this population.