Comprehensive Analysis of Gut Microbiota Signatures in Metastatic Colorectal Cancer

Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. About 1 in 4 people with CRC already have cancer spread (metastasis) when first diagnosed, and about half develop spread during their illness. Recent research shows that bacteria living in the gut and even within tumors might play an important role in how cancer spreads.

The goal of this study is to better understand how bacteria might influence the spread of colorectal cancer. The main questions the investigators aim to answer are:

Are there differences in bacteria between people whose cancer has spread and those whose cancer has not spread? Could certain bacteria help predict which cancers might spread?

To answer these questions, the investigators will:

Collect different types of samples from participants:

Tumor tissue Normal tissue near the tumor Tissue from where cancer has spread Stool samples before surgery Study the bacteria in these samples using advanced testing methods Compare bacterial patterns between different groups

People can take part in this study if they:

Are between 18 and 75 years old Have colorectal cancer confirmed by doctors Have not taken antibiotics recently Do not have immune system problems

This research may help us:

Understand why some colorectal cancers spread Find new ways to predict which cancers might spread Develop better treatments for colorectal cancer

Study Overview

• Status: Recruiting
• Conditions: Rectal Neoplasms; Colon Neoplasms; Metagenome; Microbiota
• Intervention / Treatment: Procedure: Biospecimen Collection Procedure

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Lu Xiang'en; Phone Number: +86-020-38379764; Email: zslylib@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • The Sixth Affiliated Hospital of Sun Yat-sen University
      • Contact: Huai'ming Wang; Phone Number: +86-020-38254052; Email: wanghm7@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll patients aged 18-75 years with pathologically confirmed colorectal cancer treated at the Sixth Affiliated Hospital of Sun Yat-sen University. Participants will be divided into two main groups: those with peritoneal metastasis (metastasis group) and those without distant metastasis (non-metastasis group). The study population will include both male and female patients who meet all inclusion criteria and none of the exclusion criteria. All participants must have clearly defined clinical staging and be scheduled for surgical treatment, with an expected survival of at least 3 months. Patients with recent use of antibiotics, probiotics, or immunosuppressants, those with intestinal obstruction or perforation, and those with other severe comorbidities will be excluded.

Description

Inclusion Criteria:

• Age between 18 and 75 years
• Pathologically confirmed colorectal cancer
• Clearly defined clinical staging: including imaging or pathologically confirmed metastatic colorectal cancer (stage M1) and colorectal cancer without distant metastasis (stage M0)
• Expected survival ≥ 3 months
• Voluntary participation and signed informed consent

Exclusion Criteria:

• Use of probiotics, antibiotics, or immunosuppressive agents within 1 month before surgery
• Preoperative complete intestinal obstruction or gastrointestinal perforation
• Intraoperative gastrointestinal perforation or tumor rupture
• Previous history of gastrointestinal surgery (excluding colorectal cancer surgery, appendectomy, and cholecystectomy) or concurrent severe gastrointestinal diseases such as inflammatory bowel disease
• Concurrent active systemic immune or infectious diseases, including severe allergies, rheumatoid arthritis, systemic lupus erythematosus, viral hepatitis, acquired immunodeficiency syndrome, etc.
• Concurrent unhealed primary malignant tumors
• Severe organ dysfunction or failure
• Other conditions deemed unsuitable for this study by the investigator

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HC; Healthy individuals without colorectal cancer or other cancers Will provide stool samples Matched by age and gender with cancer groups	Procedure: Biospecimen Collection Procedure; Collection of fecal samples from healthy volunteers, non-metastatic (M0) and metastatic (M1) colorectal cancer patients. Additionally, collection of tissue samples during surgery from operable patients (M0 and M1) for subsequent research analysis.
nmCRC; Participants with colorectal cancer without distant metastasis (M0 stage) Confirmed by imaging studies and/or pathological examination Will provide primary tumor tissue, adjacent normal tissue, and stool samples	Procedure: Biospecimen Collection Procedure; Collection of fecal samples from healthy volunteers, non-metastatic (M0) and metastatic (M1) colorectal cancer patients. Additionally, collection of tissue samples during surgery from operable patients (M0 and M1) for subsequent research analysis.
mCRC; Participants with colorectal cancer with distant metastasis (M1 stage) Confirmed by imaging studies and/or pathological examination Will provide primary tumor tissue, metastatic tumor tissue, adjacent normal tissue, and stool samples	Procedure: Biospecimen Collection Procedure; Collection of fecal samples from healthy volunteers, non-metastatic (M0) and metastatic (M1) colorectal cancer patients. Additionally, collection of tissue samples during surgery from operable patients (M0 and M1) for subsequent research analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal Microbiota Diversity Differences Between Colorectal Cancer Patients With and Without Peritoneal Metastasis	Comparison of microbial diversity between metastasis and non-metastasis groups, including alpha diversity (Chao1 index for species richness, Shannon index for species diversity) and beta diversity (Bray-Curtis distance, UniFrac distance). These measurements will evaluate differences in intestinal microbiota composition related to colorectal cancer peritoneal metastasis.	Fecal samples collected at patient's first hospital admission; tissue specimens collected during surgery. All specimens analyzed within 6 months after collection.

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Publications and helpful links

General Publications

• Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, Fleck JS, Voigt AY, Palleja A, Ponnudurai R, Sunagawa S, Coelho LP, Schrotz-King P, Vogtmann E, Habermann N, Nimeus E, Thomas AM, Manghi P, Gandini S, Serrano D, Mizutani S, Shiroma H, Shiba S, Shibata T, Yachida S, Yamada T, Waldron L, Naccarati A, Segata N, Sinha R, Ulrich CM, Brenner H, Arumugam M, Bork P, Zeller G. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019 Apr;25(4):679-689. doi: 10.1038/s41591-019-0406-6. Epub 2019 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 27, 2025
• First Submitted That Met QC Criteria: August 27, 2025
• First Posted (Estimated): September 4, 2025

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: microbiota; metagenomics; rectal neoplasms; colon neoplasms
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Rectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: MCRCGM-SYSU-2025-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No