The mucosal microbiome of right-sided CRC was distinctly different from the mucosal microbiome of left-sided CRC patients, suggesting distinct microbial ecology and heterogeneous host-microbial ecologic relationships that may contribute to differences in the tumor microenvironment between left- and right-sided CRC.
Key Findings
Results
CRC was associated with alterations in both fecal and mucosal microbiomes compared to healthy controls.
Study prospectively collected 690 samples total across stool, colonic aspirate, and mucosal biopsy sample types.
Cohort comprised 32 healthy, 30 adenoma, and 31 CRC patients.
Both fecal and mucosal compartments showed microbiome differences associated with CRC status.
Results
The overall composition of the mucosal microbiome, stratified by metacommunities, differed between patients with left- and right-sided neoplastic lesions.
Mucosal biopsy samples were analyzed from patients with neoplasia at different anatomic locations.
Metacommunity-based stratification revealed distinct overall compositional differences between left- and right-sided disease.
This heterogeneity suggests distinct microbial ecology depending on tumor anatomic location.
Results
Patients with right-sided CRC had an elevated inter-phylum ecologic network compared to left-sided CRC.
Right-sided CRC was characterized by increased ecological interactions between microbial phyla.
This finding suggests a more complex or interconnected microbial community structure in right-sided tumors.
The inter-phylum ecologic network difference distinguishes right-sided CRC at an ecological rather than purely taxonomic level.
Results
Patients with left-sided CRC had an enriched abundance of Fusobacterium compared to right-sided CRC.
Fusobacterium enrichment was specifically associated with left-sided colorectal neoplasia.
This finding contrasts with the inter-phylum network elevation seen in right-sided CRC.
Fusobacterium is a previously reported CRC-associated taxon, here shown to have anatomic site specificity.
Results
Rectal neoplasia harbored a tumor microbiome that was distinctly different from the tumor microbiome at other anatomic sites.
The rectum represented a unique microbiome niche separate from both left-sided (non-rectal) and right-sided CRC.
This finding highlights intra-colorectal heterogeneity extending beyond a simple left-right dichotomy.
Rectal tumors may therefore represent a distinct microbiome-defined subtype of colorectal neoplasia.
Methods
Multiple sample types—stool, colonic aspirate, and mucosal biopsy—were collected to comprehensively profile the intestinal microbiome across compartments.
A total of 690 samples were collected prospectively across three sample types.
This multi-compartment approach allowed comparison of luminal versus mucosal microbial communities.
What This Means
This research suggests that the community of microbes living in and around colorectal tumors is not uniform—it varies significantly depending on where in the colon or rectum a tumor is located. The researchers collected nearly 700 samples (stool, gut fluid, and tissue biopsies) from healthy individuals, patients with precancerous polyps (adenomas), and patients with colorectal cancer (CRC). They found that colorectal cancer overall is associated with changes in the gut microbiome, but more importantly, the microbial patterns in tumors on the right side of the colon were distinctly different from those on the left side. Right-sided tumors showed more complex interactions between different groups of bacteria (elevated inter-phylum ecological networks), while left-sided tumors had higher levels of a specific bacterium called Fusobacterium, which has previously been linked to colorectal cancer. Rectal tumors were found to have their own unique microbial profile, different from tumors elsewhere in the colon.
These findings matter because left- and right-sided colorectal cancers are already known to behave differently clinically—they respond differently to treatments and have different survival outcomes. This research suggests that the microbial environment of the tumor may be one reason for these differences. Understanding how bacteria differ between tumor locations could help explain why these cancers behave differently and might eventually point toward location-specific diagnostic markers or treatments. The study also highlights that using multiple types of samples (stool, tissue, gut fluid) gives a more complete picture of these microbial communities than any single sample type alone.
Wong S, Kwong T, Zhang R, Lam T, Ho A, Leung W, et al.. (2026). Comprehensive microbiome profiling reveals mucosal microbiome heterogeneity in patients with left- and right-sided colorectal neoplasia.. Cancer biology & medicine. https://doi.org/10.20892/j.issn.2095-3941.2025.0846