The Gut Virome as a Trigger for IBD: From Metagenomics to Pathogenesis

NCT05906680 | Unknown

• 1 other identifier: IBDomic
• Study Type: observational
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Alterations in the composition of the intestinal microbiota (dysbiosis) are well known involved in the pathogenesis of gastrointestinal disorders, such as inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). While bacteria have always gotten the most attention in gastrointestinal disorders, the viral component of the human gut microbiome, called the "gut virome", is underestimated. In addition to bacteriophages, the gut virome also harbors viruses that infect eukaryotic cells, capable of transferring their information directly to host cells, and associated with the pathogenesis of both UC and CD. Although a substantial number of studies have described the viral composition of gut microbiota in human feces, it is necessary to define the entire eukaryotic virome which colonizes the intestinal mucosa of patients with inflammatory bowel disease and which intestinal cell population is most affected. Therefore, this study aims at a comprehensive metagenomic analysis on single cells of the intestinal mucosa from a large cohort of treatment-naïve young patients with IBD at their first diagnosis to find out which cells are affected by eukaryotic viruses in the early stages of the onset of IBD and how it can affect the immune response of the mucosa, eventually leading to chronic intestinal inflammation.

Conditions

IBD

Keywords

Gut virome; Intestinal Bowel Disease

Outcome Measures

Primary Outcomes (1)

• Characterization of the gut virome

  To collect and characterize scpRNAseq-transcriptomes derived from intestinal mucosa of early-diagnosed, treatment naïve young IBD patients

  13 months

Study Arms (3)

Ulcerative Colitis (UC)

Patients with ulcerative colitis undergoing endoscopy and biopsies-collection according to the standard of care. First diagnosis for UC, treatment naive patients (≥18 and \<40 years), with no previously documented gastrointestinal infections. Furthermore, clinical and endoscopic evaluation (Mayo score≥2).

Procedure: Additional biopsies collection

Crohn's Disease (CD)

Patients with Crohn's disease undergoing endoscopy and biopsies-collection according to the standard of care. First diagnosis for CD, treatment naive patients (≥18 and \<40 years), with no previously documented gastrointestinal infections. Furthermore, clinical and endoscopic evaluation (Harvey-Bradshaw score≥5 and overall Simplified Endoscopic Score (SES-CD)\> 2).

Procedure: Additional biopsies collection

No UC and CD

Subjects undergoing endoscopy and biopsies-collection according to the standard of care (≥18 and \<40 years) (for example patients in screening for colorectal cancer disease). Subjects not affected by UC or CD according to the previously reported clinical and endoscopic evaluation criteria.

Procedure: Additional biopsies collection

Interventions

Additional biopsies collection PROCEDURE

We will recruit only subjects (UC, CD and NO-UC/CD) scheduled for the endoscopy and biopsies-collection according to the usual clinical practice. During the endoscopy we will collect 6 additional biopsies.

Crohn's Disease (CD); No UC and CD; Ulcerative Colitis (UC)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

We will recruit adult naïve patients with colitic CD or UC at their first diagnosis, ≥18 and \<40 years and without any previously documented gastrointestinal infections in collaboration with the Gastroenterology and Digestive Endoscopy unit (IRCSS Ospedale San Raffaele). CD and UC diagnosis will be determined by clinical and endoscopic scores (described in inclusion criteria). Control data will come from the same intestinal areas of age-matched no-UC/CD subjects undergoing endoscopic surveillance for not IBD-related conditions according to the standard of care. The participation is voluntary and the patient is allowed to refuse further participation in the protocol whenever he/she wants.

You may qualify if:

• SUBJECTS AFFECTED BY UC OR CD:
• subjects undergoing endoscopy and biopsies-collection according to the standard of care first diagnosis for UC or CD, treatment naive patients (≥18 and \<40 years)
• no previously documented gastrointestinal infections
• Furthermore, for subjects with UC:
• \- clinical and endoscopic evaluation (Mayo score≥2)
• Furthermore, for subjects with CD:
• \- clinical and endoscopic evaluation (Harvey-Bradshaw score≥5 and overall Simplified Endoscopic Score (SES-CD)\> 2)
• SUBJECTS NOT AFFECTED BY UC OR CD (CONTROL GROUP):
• subjects undergoing endoscopy and biopsies-collection according to the standard of care (≥18 and \<40 years) (for example patients in screening for colorectal cancer disease.)
• subjects not affected by UC or CD according to the previously reported clinical and endoscopic evaluation criteria
• All patients will be asked to sign the written informed consent.

You may not qualify if:

• SUBJECTS AFFECTED BY UC OR CD:
• subjects with UC or CD who do not respect the clinical and endoscopic evaluation criteria previously described
• subjects with UC or CD who respect the clinical and endoscopic evaluation criteria BUT previously treated with/undergoing anti-inflammatory and/or immunosuppressive drugs
• SUBJECTS NOT AFFECTED BY UC OR CD (CONTROL GROUP):
• \- subjects undergoing anti-inflammatory and/or immunosuppressive treatments for other diseases not related to UC or CD

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, Italy

RECRUITING

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Gastroenterologist

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 18, 2023
• Study Start: February 7, 2023
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)