Introduction

The global burden of Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is increasing. Due to its chronic nature, IBD entails long-term healthcare resource use, contributing to substantial economic and environmental costs. Digestive endoscopy, while a cornerstone of disease monitoring, is associated with high energy consumption, greenhouse gas (GHG) emissions, and medical waste. Intestinal ultrasound (IUS) has emerged as a non-invasive, accurate, and potentially more sustainable alternative.

Aims & Methods

The present study aimed to compare the environmental impacts in terms of CO₂ emissions, energy consumption (kWh), and disposable waste of IUS and endoscopy for therapeutic monitoring in IBD. In this single-center, retrospective observational study conducted at IRCCS Humanitas Research Hospital (Rozzano, Milan), all consecutive IUS and lower gastrointestinal endoscopies performed for therapeutic monitoring in IBD patients between January 2022 and December 2025 were included. Procedures for oncologic surveillance in long-standing disease, isolated rectal involvement (<15 cm from the anal verge), or without confirmed IBD were excluded. Clinical and procedural data were collected. Environmental metrics such as CO₂ emissions, energy consumption (kWh), and disposable waste were estimated using validated conversion factors and compared using appropriate statistical tests (Independent-samples t-test or Mann–Whitney U test).

Results

Endoscopic procedures performed during study period (n=2698) ↓ Exclusion criteria - Endoscopic procedures in trial setting (n=1157) -Endoscopic surveillance in UC (n= 216) -Pouchoscopies & ulcerative proctitis monitoring (n=162) - Operative/ emergency procedures (n=71) ↓ Endoscopic procedures included in the analysis (n=1092) Colonoscopies (n= 710)↵ ↳ Sigmoidoscopies (n=382)

intestinal ultrasounds performed during study period (n=1541) ↓ Exclusion criteria - Indications other than disease monitoring/ patient BMI> 30 Kg/m2 (n= 231) ↓ Intestinal ultrasounds included in the analysis (n=1310) ​

Flowchart 1. Visual representation of the process of selecting procedures to be included in the final analysis. UC: Ulcerative colitis; BMI: Body Mass Index.

During the study period, a total of 1092 endoscopic procedures, comprising 710 colonoscopies and 382 sigmoidoscopies, along with 1310 IUS were performed in 1028 IBD patients (58% UC, 42% CD). Estimated resource use for all endoscopic procedures totaled 1,256 kWh of electricity, 72,080 L of CO₂ emissions, and 585.6 kg of disposable waste, based on procedural averages (~1.5 kWh, 80 L of CO₂, 650 g waste per colonoscopy; ~50% of values for sigmoidoscopies). In contrast, IUS was associated with an estimated 524 kWh of electricity and 196.5 kg of disposable waste (average ~0.4 kWh, almost no CO₂ consumption, 150 g waste per exam). Compared to endoscopy, IUS reduced energy use by 82%, CO₂ emissions by 95%, and waste generation by 66% (P < 0.05 for all comparisons).

Conclusion

While gastrointestinal endoscopy remains indispensable in certain clinical scenarios, its environmental impact is considerable. In contrast, IUS emits almost no equivalent of CO₂, consumes significantly less energy per examination and produces negligible wastes. For therapeutic monitoring in IBD, IUS has demonstrated high diagnostic accuracy with a markedly lower ecological footprint. These findings promote IUS as a sustainable and environmentally friendly alternative for routine IBD monitoring in appropriate scenarios.

Disclosure

A Armuzzi has received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi Tanabe, Novartis, Pfizer, Roche, Sandoz, Takeda, Tigenix, and research grants from MSD, Pfizer, Takeda and Biogen. A Repici received consulting fee from Medtronic, Fuji and Olympus and has received research grant from Alfa Sigma, Norgine, Boston and Erbe. C Bezzio received speaker’s fees and consulting fees from for Takeda, MSD, Ferring, Abbvie, Galapagos and Janssen. A Dal Buono has received speaker’s fees from Pfizer, MSD, Eli-Lilly, Celltrion, Janssen, and consulting fees from Ferring. R Gabbiadini has received speaker’s fees from Pfizer, MSD, Ferring, Eli-Lilly, Celltrion, Janssen, consulting fees from Pfizer and Abbvie. G. Privitera has received speaker’s fees from Janssen and Alphasigma. B. Masoni and G. Franchellucci declare no conflict of interests.

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.