Fusobacterium nucleatum: a transboundary pathogen in host-microbiota networks 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 reviewed?
This review discusses the pathogenic mechanisms of Fusobacterium nucleatum (Fn), a Gram-negative anaerobic bacterium with a dual role as a commensal and opportunistic pathogen. The article synthesizes the bacterium’s involvement in various diseases, particularly colorectal cancer (CRC), inflammatory bowel disease (IBD), periodontal disease, and systemic pathologies such as atherosclerosis, arthritis, and preterm birth. The review explores the molecular mechanisms, virulence factors (VFs), microbial interactions, and ecological dynamics that enable Fn to transition from a local pathogen to a systemic one, proposing a “transboundary pathogen” model.
Who was reviewed?
The review examines the research on Fusobacterium nucleatum, focusing on its subspecies-specific virulence factors, tissue-specific colonization patterns, and its impact on host immunity and disease progression. It also discusses the complex interactions of Fn with other microorganisms, including both synergistic and antagonistic relationships with gut microbiota, and its role in promoting diseases through biofilm formation, immune modulation, and metabolic changes.
What were the most important findings?
The review underscores the significant role of Fusobacterium nucleatum in driving systemic diseases through its “transboundary” pathogenicity. This bacterium breaches mucosal barriers, such as in the oral cavity and gut, and disseminates to distal organs, including the liver, brain, and joints, thereby influencing diseases like CRC, IBD, and even Alzheimer’s disease. Its virulence factors, such as adhesins (e.g., FadA, Fap2), outer membrane vesicles (OMVs), and metabolic products like hydrogen sulfide and butyrate, are central to its ability to invade tissues, modulate immune responses, and promote tumor progression. In CRC, Fn’s presence contributes to tumor progression through immune evasion mechanisms, including immune checkpoint modulation. The bacterium forms synergistic biofilms with other pathogens like Clostridioides difficile and Pseudomonas aeruginosa, enhancing infection severity. Additionally, Fn-derived metabolites such as butyrate and hydrogen sulfide show context-dependent roles, either promoting inflammation and tumorigenesis or exerting protective effects. Probiotics like Lactobacillus rhamnosus and Akkermansia muciniphila can antagonize Fn, making them potential therapeutic agents.
What are the greatest implications of this review?
The greatest implication of this review is its potential to reshape therapeutic strategies targeting Fusobacterium nucleatum in microbiota-driven diseases. Understanding the bacterium’s role in both local and systemic disease pathways highlights the need for precision medicine approaches. By targeting Fn’s virulence factors and modulating the gut microbiota, particularly through probiotics or bacteriocin production, clinicians could mitigate the progression of diseases associated with Fn, such as CRC, IBD, and systemic inflammation. Additionally, the review suggests that monitoring specific metabolites and microbial interactions in clinical settings could aid in early detection and personalized treatment regimens. However, further research is needed to fully comprehend the complex molecular mechanisms of Fn’s interactions with the host and its role in cancer resistance, opening the door for future interventions targeting microbial communities to improve clinical outcomes.
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.