Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types—bacteria, viruses, fungi, protozoa, and archaea—plus major pathogenic and beneficial examples.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study examined the role of Fusobacterium nucleatum in colorectal cancer (CRC) chemoresistance. The researchers investigated how F. nucleatum influences autophagy in CRC cells and contributes to chemoresistance to common chemotherapy agents like Oxaliplatin and 5-fluorouracil (5-FU). Using in vitro and in vivo models, the study focused on the mechanisms by which F. nucleatum activates autophagy, particularly through the loss of microRNAs miR-18a* and miR-4802, and its impact on chemotherapy efficacy.
Who was studied?
The study involved CRC cell lines, specifically HCT116 and HT29 cells, which were co-cultured with F. nucleatum to assess its effects on autophagy and chemoresistance. Additionally, animal models (xenograft mouse models) were used to evaluate tumor responses to chemotherapy in the presence of F. nucleatum. The study also included clinical observations, comparing CRC tissues from patients with high and low levels of F. nucleatum to assess the correlation with miRNA levels and autophagy activation.
What were the most important findings?
The most significant finding of this study was that F. nucleatum promotes CRC chemoresistance by activating the autophagy pathway. This was shown through increased expression of autophagy-related proteins (e.g., ULK1 and ATG7) and the conversion of LC3-I to LC3-II, a marker of autophagy activation. Furthermore, the presence of F. nucleatum in CRC cells led to a selective loss of miR-18a* and miR-4802, which are known to regulate autophagy-related genes. This loss contributed to the activation of the autophagy pathway, which in turn helped CRC cells resist chemotherapy-induced apoptosis. The study also demonstrated that inhibition of autophagy, through either pharmacological inhibitors (like Chloroquine) or genetic silencing of key autophagy genes (ULK1 and ATG7), enhanced the sensitivity of F. nucleatum-treated CRC cells to chemotherapy. In clinical samples, a higher amount of F. nucleatum correlated with poor prognosis and recurrence in CRC patients, reinforcing the bacterium’s role in chemoresistance.
What are the greatest implications of this study?
The findings highlight F. nucleatum as a key factor in CRC chemoresistance, suggesting that targeting autophagy could be a potential therapeutic strategy to improve chemotherapy outcomes in CRC patients. The study also implies that assessing the levels of F. nucleatum in CRC tumors could serve as a diagnostic or prognostic tool to predict patient response to chemotherapy. Moreover, the identification of miR-18a* and miR-4802 as modulators of chemoresistance offers potential avenues for developing molecular therapies to counteract the protective effects of autophagy induced by F. nucleatum.
Fusobacterium nucleatum
Fusobacterium nucleatum is a Gram-negative, anaerobic bacterium commonly found in the oral cavity, where it plays a crucial role in the formation of biofilms. Beyond its presence in the mouth, Fn is implicated in a variety of systemic conditions, including periodontal disease, colorectal cancer, and inflammatory bowel disease. Known for its ability to coaggregate with other bacteria, Fn's pathogenic potential is magnified in dysbiotic microbial communities, making it a key player in polymicrobial infections. The bacterium utilizes multiple virulence factors such as FadA and Fap2, which facilitate adhesion to host tissues and immune evasion, ultimately contributing to its role in chronic and inflammatory diseases.