Microbiota: Its Role in Chronic Inflammation, IDB and Risk of Colorectal Cancer. Evaluation of a Predictive Prognostic Model With Therapeutic Implications

NCT ID: NCT07106463

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-08-30
• Study Completion Date: 2026-08-29

Brief Summary

The gut microbiome is emerging as a crucial factor in several intestinal diseases, contributing to the etiopathogenesis of inflammatory disorders. While most microorganisms reside in the gut and play vital roles in host immunity and nutrition, an imbalance in microbiome composition can trigger chronic intestinal inflammation, increasing the risk of developing colorectal cancer (CRC). Significant quantities of the Gram-negative bacterium Fusobacterium nucleatum have been associated with poorer survival rates and increased resistance to chemotherapy in CRC patients. Furthermore, F. nucleatum has been shown to mediate CRC chemoresistance through activation of the ULK1 autophagy pathway. Recent studies have reported the ability of F. nucleatum to induce inflammation in the gut epithelium and activate a specific component of the immune system, the NLRP3 inflammasome, leading to the release of IL-1ß, a pro-inflammatory cytokine. The aim of this project is to investigate the role of F. nucleatum in the development of chronic inflammatory bowel disease (IBD) and CRC by exploring a potential connection between its involvement in NLRP3 inflammasome activation and its ability to promote chemoresistance through autophagy modulation. The working hypothesis posits that these two biological processes are strongly interconnected and may significantly influence the interaction between the gut microbiota and host immunity, ultimately affecting disease progression in IBD and CRC. The proposed research plan includes:

i) in vitro characterization of the impact of F. nucleatum infection on NLRP3 inflammasome activation, autophagy induction, and CRC development and progression; ii) determination of the correlation between F. nucleatum abundance and chronic IBD, as well as early and advanced stages of colorectal carcinomas; iii) implementation of radiomic analyses to accurately distinguish cancerous from non-cancerous colon tissue and to identify radiomic signatures indicative of specific tumor-host interactions, including inflammation and/or autophagy. This research aims to generate novel insights into the interplay between the microbiota and chronic degenerative diseases, thereby contributing to the development of innovative microbiota-based therapeutic strategies. This proposal may represent an effective approach to predict patient outcomes and improve the prognosis of individuals with IBD and CRC by enabling differential patient management, correlating F. nucleatum levels with inflammation and autophagy, and potentially informing combinatorial treatments to overcome chemoresistance.

Conditions

IBD (Inflammatory Bowel Disease); Colon Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

Individuals in generally good health

Individuals diagnosed with Inflammatory Bowel Disease (IBD)

Individuals diagnosed with early-stage Colorectal Cancer (CRC)

Individuals with locally advanced Colorectal Cancer (CRC)

Individuals with metastatic Colorectal Cancer (CRC)

Exclusion Criteria

Individuals diagnosed with other malignancies

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Messina

OTHER

Sponsor Role: lead

Responsible Party

Massimiliano Berretta

Full Professor of Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Azienda Ospedaliera Universitaria "G.Martino"

Messina, Italy, Italy

Countries

Italy

Other Identifiers

07-24

Identifier Type: -

Identifier Source: org_study_id