Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease where accurate assessment of disease activity is essential for effective patient management. Endoscopy is the gold standard for evaluating mucosal inflammation, but non-invasive alternatives, such as transabdominal ultrasound (TAUS), are garnering interest.

Aims & Methods

This study aimed to evaluate the sensitivity of rectal wall thickness measurements using TAUS in assessing disease activity in ulcerative colitis, and to identify an ideal cut-off threshold by comparing results with endoscopic and histological findings.
In a prospective, observational study, we enrolled consecutive patients with UC who were referred to our tertiary center from May 2024 to April 2025. Eligibility required a scheduled TAUS within 30 days of a staging colonoscopy, without intervening therapy adjustments. Exclusion criteria included technically inadequate TAUS readings (e.g., due to anatomical variations or excessive gas interposition) and minor-aged patients. Each patient underwent TAUS performed by a single, experienced operator. A second experienced operator blind assessments were recorded to evaluate inter-observer variability. Rectal wall thickness was measured and compared with clinical, laboratory (CRP, fecal calprotectin), and endoscopic (MAYO score) indicators of disease activity. Histological status (active/inactive) and additional clinical data, including disease duration, extent, and therapy, were recorded.

Results

A total of 74 patients were analyzed, of whom 51.4% were female, with a median age of 55 years (IQR: 42–68). The majority presented with left-sided colitis (Montreal E2, 62.2%), followed by extensive colitis (E3, 25.7%) and proctitis (E1, 12.1%). The median disease duration was 12 years (IQR 5–23). Patients with an endoscopic MAYO score of 0 or 1 had a median rectal wall thickness of 4.95 mm (IQR 4.5–5.88), while those with a score of 2 or 3 had a median of 6.15 mm (IQR 5.3–6.7; p=0.003). Receiver Operating Characteristic (ROC) analysis for TAUS rectal wall thickness showed good discriminatory ability for endoscopic activity (cut-off: 5.55 mm, AUC 0.725, 95CI 0.597-0.853, Se 0.80, Sp 0.71), comparable to fecal calprotectin (cut-off: 277 µg/g, AUC 0.717, 95CI 0.589-0.845, Se 0.70, Sp 0.66; p=0.256) and superior to CRP (cut-off: 1 mg/L, AUC 0.511, 95CI 0.357-0.664, Se 0.50, Sp 0.50; p<0.0001). For histological activity, TAUS again performed well (cut-off: 5.55 mm, AUC 0.794, 95CI 0.682-0.906, Se 0.76, Sp 0.80), closely matching fecal calprotectin (cut-off 302, AUC 0.744, 95CI 0.627-0.861, Se 0.69, Sp 0.73; p=0.425) and outperforming CRP (cut-off 1.5, AUC: 0.631, 95CI 0.497-0.765, Se 0.62, Sp 0.63; p<0.0001). Inter-observer agreement for TAUS rectal wall thickness was excellent, with an intraclass correlation coefficient of 0.923 (p<0.0001), underscoring the reproducibility of this non-invasive method.

Conclusion

TAUS measurement of rectal wall thickness demonstrates promising sensitivity and reproducibility in detecting mucosal and histological activity in UC, aligning closely with established markers such as fecal calprotectin. A cut-off value of 5.55 mm showed good discriminatory performance in this cohort, suggesting potential utility as a non-invasive marker of disease activity..Given its non-invasive nature, low cost, and strong inter-observer agreement, TAUS is a valuable adjunct for routine UC monitoring. Combined with clinical and biochemical data, it may reduce the need for repeated endoscopy, minimizing patient burden, healthcare costs, and environmental impact.

Introduction

Genetic variants associated to a higher risk of developing eosinophilic esophagitis (EoE) and other atopic conditions have been described. However, no study has investigated how these genetic variants influence clinical features of EoE or the atopic concomitances that usually accompanied this disease.

Aims & Methods

This study aims to assess whether single nucleotide polymorphisms (SNPs) in genes related to EoE and atopies associate with disease features and atopic concomitances in a large, representative cohort. Patients diagnosed of EoE according to clinical guidelines were recruited from 4 Spanish referral hospitals and demographical and clinical data were obtained both retrospectively and prospectively. The concomitant atopies analyzed were rhinitis, conjunctivitis, asthma, dermatitis and any food allergy. The recruited cohort was randomly divided into discovery (DC) and validation cohorts (VC) (70% and 30%, respectively). Genotyping was performed using an Open Array platform with 60 SNPs on DNA obtained from peripheral blood. Chi-square or Fisher’s exact test were used for statistical comparisons.

Results

Overall, 647 patients (74.7% male, 32.4±15.2 mean age) were included; 81% of them with an inflammatory phenotype. Rhinitis was the most common atopy (55.8%), while dermatitis was the least frequent (17.5%). Food allergy was documented in 28% of patients.
In relation to EoE characteristics, four SNPs were initially associated with endoscopic findings (measured by EREFS score) and with peak eosinophil counts in esophageal biopsies within the discovery cohort. However, only rs77569859 in the CAPN14 gene remained statistically significant in the validation cohort. TC and CC genotypes of this variant, present in 23.7% of the cohort, were associated with lower EREFS score under a dominant model (3.30±1.60 vs 2.92±1.66, p=0.011 DC/0.002 VC). Additionally, rs76562819, also in CAPN14 gene, showed a trend toward a lower peak eosinophil count per high power field (47.7±24.4 vs 66.6±48.3, p=0.005 DC/0.116VC) under a recessive model (AG and GG genotypes in 11.3% of our patients).
Regarding atopic comorbidities, rs1800925-TT in IL13 (found in 5.7% of our patients) was associated a higher prevalence of conjunctivitis (60% vs 39% in the overall cohort, p=0.020 DC/0.057 VC) and showed a trend toward increased asthma prevalence (54% vs 35%, p=0.056 DC/0.155 VC). A weaker association with asthma was observed for STAT6 rs324015, with an increased prevalence in patients with AG and GG genotypes (41% vs 32%, p=0.079 DC/0.162 VC; present in 34.9 % of the cohort). For dermatitis, a protective effect was seen in patients with the TT genotype of rs2032582 in ABCB1 gene (found in 16.1% of our patients), as the prevalence decreased from 19% to 8% (p=0.033 DC/0.157 VC). No consistent associations were found for rhinitis or food allergy with any SNP across both cohorts.

Conclusion

We have identified significant associations between genetic variants and both clinical features and atopic comorbidities in Spanish patients with EoE, highlighting the potential of genetic profiling to improve clinical characterization and patient management.

Introduction

Colorectal cancer (CRC) is the third commonest malignancy globally & the second leading cause of cancer mortality. Prognosis is highly stage-dependent, with survival exceeding 85% for early-stage diagnoses but dropping sharply at advanced stages. While national screening programs have reduced mortality in older populations, incidence in younger individuals is rising, often accompanied by delays in diagnosis. Existing non-invasive approaches, such as quantitative faecal immunochemical (qFiT) testing & blood-based liquid biopsies, provide limited sensitivity, particularly for pre-malignant or early-stage disease, leaving colonoscopy as the invasive gold standard. Because CRC is a mucosal disease, rectal mucus represents an under-explored biospecimen enriched for exfoliated cells, DNA, & microbial material, potentially enabling early & minimally invasive detection.

Aims & Methods

We assessed rectal mucus sampling as a novel diagnostic approach for CRC & adenomatous polyps. Using the OriCol™ device, rectal mucus was retrieved from 800 participants from 4 NHS colorectal surgical outpatients clinics without the need for bowel preparation (July 2020 - October 2023). A hologenomic strategy was applied, integrating three complementary laboratory pipelines: error-corrected next-generation sequencing for somatic mutations (n=161), enzymatic methyl-sequencing for DNA methylation profiling (n=208), & whole-genome shotgun metagenomics for microbiome characterisation (n=379). Data underwent rigorous quality control, with feature selection & integrative multi-omics analysis used to identify clinically informative biomarkers, stratify pathology by site & stage, and evaluate diagnostic potential.

Results

Distribution of CRC was 24% right-colon, 23% hepatic-splenic flexure, 18% left-colon, 35% rectal. Somatic mutation analysis revealed pathogenic variants in well-known CRC drivers including TP53, APC, KRAS, BRAF, ERBB2, FBXW7, PIK3CA & SMAD4, with mutation allele frequencies representing disease state. DNA methylation profiling demonstrated widespread hypermethylation at CpG islands near promoters and transcription start sites, particularly in SDC2, LRRC4, PPP2R5C & RNF217, with gradients of signal strength from rectal to right-sided cancers & from CRC to advanced adenomas (>10mm +/- HG dysplasia), to early polyps/normal controls. Microbiome profiling identified 94 species associated with CRC, including previously reported taxa such as Fusobacterium nucleatum & Hungatella hathewayi, alongside novel associations with Clostridium scindens & Anaerotruncus colihominis. Multi-omics integration markedly improved diagnostic resolution, clustering CRC & advanced adenomas polyps separately from controls, with early-stage polyps occupying an intermediate position.

Conclusion

We established rectal mucus as a rich biospecimen for minimally invasive CRC diagnostics. By combining host genetic & epigenetic markers with microbial signatures, the hologenomic approach provides sensitive detection of pre-cancerous lesions & stratification by site/stage, outperforming single-modality assays. Importantly, local mucosal sampling enabled discovery of novel microbial-pathology associations not detectable in stool-based studies. These findings demonstrate the translational potential of rectal mucus hologenomics as a scalable diagnostic platform, offering a non-invasive alternative for triaging symptomatic patients & potentially extending to screening programmes. Further clinical validation is underway to refine performance metrics & benchmark against existing diagnostic standards (ORICOL-EGI-04 Study NCT06649123).

References

Complete references for this work are listed in the accepted Nature Communications paper

Disclosure

1. This work has been accepted for publication in Nature Communications and is currently embargoed whilst final editing is completed. A letter of confirmation of acceptance for publication can be provided.
2. The study is funded and performed through Origin Sciences Ltd with many of the staff holding share options in the company. The clinical research teams were provided with educational grants from Origin Sciences Ltd to fund the research and support research fellows and nurses.
3. Rectal mucus samples and tumour tissues were collected following UK Health Regulatory Authority (HRA) and Ethics Committee approvals (IRAS 263745, 19/EM/0266). Written informed consent was obtained from all donors. All samples were collected from patients enrolled in the ORI-EGI-02 study; Exploratory Study of Rectal Mucus for Diagnosing Disease (NCT04659590) from four NHS Hospitals.
4. The presenting author is employed by the NHS as a Consultant Colorectal Surgeon and is Chief Medical Officer, Origin Sciences and holds share options with the company.