Fusobacterium nucleatum drives colorectal cancer progression through bone marrow-derived immune cell recruitment and NLRP3-dependent inflammatory microenvironment induction, as Fn failed to induce tumor growth in NLRP3-/- mice.
Key Findings
Results
Fusobacterium nucleatum administration significantly increased tumor growth in two colorectal cancer mouse models compared to controls.
Two CRC mouse models were employed: subcutaneous MC38 model and AOM-DSS orthotopic model.
Fn was administered via intratumoral injection or oral gavage, with Streptococcus mutans and normal saline used as comparators.
Quantitative PCR confirmed elevated Fn abundance in CRC tissues from both mouse models and human specimens.
Tissue specimens were also collected from healthy volunteers, patients with ulcerative colitis, colorectal adenoma, and CRC to assess Fn abundance across disease stages.
Results
Fn reshapes the tumor immune landscape toward a proinflammatory state by enriching myeloid-derived immune cells.
Immunofluorescence analysis showed enrichment of myeloid cells marked by CD45/CD11b, CD11C, F4/80, MHCI, and MHCII in tumors of Fn-treated mice.
In vitro and in vivo experiments confirmed that Fn selectively expands myeloid-derived immune cells.
Flow cytometry and ELISA were used to evaluate immune cell subsets and inflammatory cytokine levels.
IHC and FISH were used to detect inflammatory cytokines and immune cells in tumor tissues.
Results
NLRP3 inflammasome activation is a key mechanism required for Fn-induced CRC progression.
Fn failed to induce tumor growth in NLRP3-/- mice, establishing NLRP3 as mechanistically necessary for Fn-driven tumor promotion.
Western blot was used to examine NLRP3 inflammasome and other protein expression.
This finding confirms that Fn's pro-tumorigenic effects are dependent on NLRP3-mediated inflammatory signaling rather than direct bacterial cytotoxicity alone.
Results
Fn administration produced distinct alterations in the gut microbiota composition of treated mice.
16S rRNA amplicon sequencing was used to analyze Fn-mediated alterations in mouse gut microbiota.
Microbiome analysis revealed distinct bacterial clades in Fn-treated mice compared to controls.
Fn is a gram-negative oral bacterium that was found to exist in the intestine and exert pro-tumorigenic effects consistent with gut microbiota imbalance in CRC.
Results
Fn abundance was elevated in human colorectal cancer tissues, with Fn detected across the spectrum from healthy tissue through ulcerative colitis, colorectal adenoma, and CRC.
Tissue specimens were collected from healthy volunteers, patients with ulcerative colitis (UC), colorectal adenoma (CRA), and CRC at the First Affiliated Hospital of Henan University of Science and Technology.
Specimens were obtained via colonoscopy and surgical resection.
qPCR was used to quantify Fn abundance in colorectal tissues across these disease categories.
What This Means
This research suggests that a bacterium normally found in the mouth, called Fusobacterium nucleatum (Fn), plays an active role in driving colorectal cancer (CRC) growth by inflaming the environment around tumors. The researchers collected tissue samples from patients with various colorectal conditions—ranging from healthy to cancer—and used two different mouse models of colorectal cancer to study how Fn affects tumor development. They found that introducing Fn into mice significantly increased tumor growth compared to mice that did not receive the bacterium, and that Fn was more abundant in cancer tissues than in healthy tissues.
A key part of this study focused on how Fn changes the immune environment inside tumors. The researchers found that Fn attracts and expands certain immune cells derived from bone marrow, pushing the tumor environment toward a chronic inflammatory state. Crucially, when they used mice that were genetically engineered to lack a protein called NLRP3—part of a cellular alarm system called the inflammasome—Fn was no longer able to promote tumor growth. This strongly suggests that Fn needs the NLRP3 inflammatory pathway to drive cancer progression.
This research matters because it helps explain one mechanism by which gut bacteria may contribute to colorectal cancer development and suggests that the NLRP3 inflammasome and the myeloid immune cells recruited by Fn could be potential targets for future cancer prevention or treatment strategies. It also highlights the broader importance of the gut microbiome in cancer biology, indicating that bacterial imbalances—not just genetic mutations—may play a meaningful role in how colorectal cancer develops and progresses.
Chen Y, Lu X, Liu K, Wen X, Du X, Zhang Y, et al.. (2026). Unveiling Fusobacterium nucleatum's role in colorectal cancer: the inflammatory microenvironment connection.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1747198