Introduction

Colonoscopic surveillance reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. Still, its invasiveness and high costs highlight the need for a non-invasive approach to predict the presence of neoplastic lesions.

Aims & Methods

This study aimed to identify faecal bacterial biomarkers to discern between carriers with colorectal lesions and those with normal colon.
Two independent Spanish cohorts (a training and a validation cohort) were recruited through two multicenter studies (Table 1). Participants provided a faecal sample before surveillance colonoscopy to quantify the abundance of F. prausnitzii (FPRA) and its phylogroups I and II (PHGI and PHGII), P. stomatis (PTST), B. fragilis (BCTF), B. thetaiotaomicron (BCTT), B46 (best BLAST match S. variabile), G. morbillorum (GMLL), B48 (best BLAST match R. faecis), and E. coli (ECO) through qPCR. Eubacteria (EUB) was quantified as the total bacterial load. Participants were classified based on colonoscopy findings as normal colonoscopy (NC), non-advanced adenoma (NAA), and advanced neoplasia (AN, including advanced adenoma and CRC). A bacterial signature for neoplasia prediction was defined and validated in the training and validation cohorts, respectively.

Table 1. Main characteristics of the study participants. NC, normal colonoscopy; NAA, non-advanced adenoma; AA, advanced adenoma; CRC, colorectal cancer.

Results

The bacterial abundances were analysed in the training cohort according to age, sex, body mass index (BMI), germline mutation, and colonoscopy findings. Significant moderate positive correlations were identified between the abundances of BCTF and age (r=0.325, p=0.040), and PHGII and BMI (r=0.399, p=0.010). A significant negative correlation was identified between GMLL abundance and BMI (r=-0.331, p=0.036). Patients harbouring MLH1 mutations exhibited a significantly higher abundance of FPRA compared to PMS2 carriers (p=0.048). Patients with neoplasia (NAA+AN) presented significantly lower abundances of BCTF (p=0.027) and B48 (p=0.038) than patients with NC. Patients with AN presented a significantly lower abundance of PTST compared to patients with NC or NAA (p=0.032).
Although all the bacterial markers achieved a sensitivity of 100% to predict the presence of neoplasia, none of them presented a specificity higher than 25% by itself. To maintain sensitivity and increase specificity a bacterial signature was defined including ECO, BCTF, GMLL, FPRA, PHGI, PHGII, and B46 combined with the inherited mutation. The signature showed 100% sensitivity (SS), 52.50% specificity (SP), 34.48% positive predictive value (PPV), and 100% negative predictive value (NPV). This signature was subsequently validated demonstrating 100% SS, 56.45% SP, 53.44% PPV, and 100% NPV.

Conclusion

A new faecal bacterial signature to predict the presence of colorectal neoplasia in LS carriers has been identified, showcasing its potential usefulness to improve and personalise LS surveillance, optimising endoscopic resources, and providing a less invasive and cost-effective approach.

Disclosure

S. Taboada-López, M. Malagón, S. Ramió-Pujol and M. Serra-Pagès are employees of GoodGut.

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

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

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