Bacteroides Fragilis and Colorectal Carcinogenesis

Bacteroides fragilis is a ubiquitous member of the human gut microbiota, comprising both non-toxigenic and enterotoxigenic strains. The latter, known as ETBF, secretes the metalloprotease Bacteroides fragilis toxin (BFT), which perturbs the colonic epithelial barrier by cleaving E-cadherin and triggering pro-inflammatory pathways. Chronic exposure to BFT promotes activation of STAT3, NF-κB and IL-17–mediated circuits, fostering a microenvironment conducive to DNA damage, enhanced cell proliferation and reduced apoptosis. Concurrently, dysbiosis characterised by overrepresentation of ETBF can modulate innate and adaptive immunity through lipopolysaccharide (LPS) signalling, altering cytokine balance within the tumour milieu. Epidemiological surveys have correlated ETBF carriage with early adenomatous lesions and higher risk of colorectal neoplasia, suggesting its value as a potential biomarker. Mechanistic studies further implicate noncoding RNAs and receptor-mediated pathways, such as RHEB/mTOR, in mediating ETBF-driven tumourigenesis. This convergence of microbial toxin activity, barrier disruption and immune modulation underpins a model in which B. fragilis acts as both instigator and amplifier of colorectal carcinogenesis. Emerging insights into these interactions inform strategies for prevention, diagnosis and microbiome-targeted interventions.

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Bacteroides Fragilis and Colorectal Carcinogenesis publication trend

The graph below shows the total number of articles in bacteroides fragilis and colorectal carcinogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Enterotoxigenic Bacteroides fragilis (ETBF): A strain of B. fragilis that produces BFT and is implicated in inflammatory and neoplastic changes in the colon.

Bacteroides fragilis toxin (BFT): A zinc-dependent metalloprotease secreted by ETBF that cleaves epithelial adhesion molecules and activates inflammatory signalling.

Dysbiosis: An imbalance in the composition or function of the gut microbiota associated with disease states.

Colonic epithelial barrier: The layer of epithelial cells lining the colon that maintains selective permeability and protects against luminal pathogens.

Pro-tumorigenic signalling: Cellular pathways, such as STAT3 or NF-κB, that promote tumour initiation, growth and survival.

References

1. Dissecting Gut‐Microbial Community Interactions using a Gut Microbiome‐on‐a‐Chip. Advanced Science (2024).
2. Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment. npj Biofilms and Microbiomes (2023).
3. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLOS ONE (2017).
4. Enterotoxigenic Bacteroides fragilis: A Possible Etiological Candidate for Bacterially-Induced Colorectal Precancerous and Cancerous Lesions. Frontiers in Cellular and Infection Microbiology (2020).
5. Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway. Cell Death & Disease (2019).