. 2025 Sep 30;11:190. doi: 10.1038/s41522-025-00818-3

Table 1.

Evidence for microorganisms as drivers of CRC: key bacteria, other bacteria, virome, and fungi

Microorganism		Epidemiological evidence	Mouse model evidence	Type of mouse model	Notes
Key Bacterial	Escherichia coli	Yes^36,37,39,43	Yes	APC^min/+³⁸ Zeb2^IEC-Tg/+⁴¹	The oncogenic potential of pks⁺ E. coli critically depends on bacterial adhesion to host epithelial cells
	Fusobacterium nucleatum	Yes^44,46	Yes	APC^min/+⁴⁵ AOM/DSS⁵¹	Fn generates abundant butyric acid, which inhibits histone deacetylase 3/8 in CD8⁺ T cells, inducing Tbx21 promoter H3K27 acetylation and expression. Furthermore, Fn-induced PD-L1 expression by activating STING signaling.
	Bacteroides fragilis	Yes⁶⁴	Yes	AOM⁶⁰ AOM/DSS^62,65 BRAF ^V600E Lgr5 ^CreMin⁶⁶	ETBF promoted CRC cell proliferation by downregulating miR-149-3p both in vitro and in vivo.
Other Bacterial	Campylobacter Species	Yes^67,69	Limited	Germ-free Apc^Min/+⁶⁸	Potentially relevant human species are C. jejuni and Campylobacter coli; evidence for the involvement of these species in human CRC is not available.
	Peptostreptococcus anaerobius	Yes⁷¹	Limited	APC^min/+^74,75,77	Its tryptophan metabolite IDA activates the aryl hydrocarbon receptor to induce ALDH1A3 expression and FSP1-mediated CoQ10 reduction, inhibiting ferroptosis via the AHR–ALDH1A3–FSP1–CoQ10 axis.
	Clostridioides difficile	Yes^78,79	Limited	APC^min/+⁸⁰	C. difficile promotes tumorigenesis by activating Wnt/β-catenin signaling, inducing ROS production, and eliciting a procarcinogenic mucosal immune response marked by IL-17 secretion and myeloid infiltration.
	Morganella morganii	Limited⁸³	Limited	AOM⁸³	Small molecules such as indolimines, produced by M. morganii, induce DNA damage and promote tumorigenesis in preclinical models.
	Streptococcus gallolyticus subspecies gallolyticus	Yes⁸⁴	Limited	AOM⁸⁵	Sgg may support CRC progression through niche adaptation mechanisms
	Akkermansia muciniphila	Yes⁹²	Limited	APCmin/+^87,89,90	A. muciniphila facilitated enrichment of M1-like macrophages in an NLRP3-dependent manner in vivo and in vitro.
virome		Yes^25,26	Limited	Apc+/1638N⁹⁸	Their direct involvement in tumorigenesis remains inconclusive.
Fungi		Yes^102–104	Limited	Limited	Despite their lower abundance and high variability among individuals, they also exhibit distinct profiles in CRC patients.

“Limited” in the Mouse model evidence column indicates that the microorganism has been investigated in vivo, but the evidence remains preliminary, with limited mechanistic clarity, a lack of consistent tumorigenic outcomes, or insufficient validation across multiple CRC models.

AOM azoxymethane, DSS dextran sodium sulfate, APC^Min/+Apc^Min heterozygous mouse model, Zeb2^IEC-Tg/+ intestinal epithelial cell-specific Zeb2 transgenic mouse, BRAF^V600E Lgr5^CreMinBraf^V600E mutant mouse under Lgr5 promoter, Germ-free Apc^Min/+ germ-free Apc^Min mouse, ETBF enterotoxigenic Bacteroides fragilis, pks+E. coliEscherichia coli strains harboring the pks genomic island encoding colibactin, FnFusobacterium nucleatum, IDA indoleacrylic acid, AHR aryl hydrocarbon receptor, ALDH1A3 aldehyde dehydrogenase 1 family member A3, FSP1 ferroptosis suppressor protein 1, CoQ10 coenzyme Q10, ROS reactive oxygen species, IL-17 interleukin-17, SggStreptococcus gallolyticus subsp. gallolyticus, Apc^+/1638NApc^+/1638N colorectal cancer mouse model.