# Fusobacteriumnucleatum: Pathophysiological and Clinical Involvement in Inflammatory Bowel Diseases, Colorectal Cancer and Cardiovascular Diseases

## TL;DR

Fusobacterium nucleatum, originally an oral bacterium, is now linked to gut and heart diseases, where it promotes inflammation and disease progression.

## Contribution

The paper systematically reviews Fusobacterium nucleatum's role in IBD, CRC, and CVD, highlighting shared pathophysiological mechanisms.

## Key findings

- Fusobacterium nucleatum promotes colorectal cancer through β-catenin activation and immune evasion.
- The bacterium exacerbates inflammatory bowel disease by disrupting intestinal barriers and inducing inflammation.
- Fusobacterium nucleatum contributes to cardiovascular disease by promoting atherosclerosis and endothelial dysfunction.

## Abstract

The oral commensal Fusobacterium nucleatum has recently been recognized as a pathobiont with systemic implications extending well beyond periodontal disease. Increasing evidence links this bacterium to inflammatory bowel diseases, colorectal cancer, and cardiovascular disorders. Its ability to adhere to epithelial and endothelial cells, modulate the immune response, and alter local metabolic and inflammatory pathways enables it to participate in disease initiation, progression, and complications. In colorectal cancer, Fusobacterium nucleatum promotes tumor growth, metastasis, and drug resistance, while in inflammatory bowel diseases, it exacerbates barrier dysfunction and chronic inflammation. In cardiovascular disease, its systemic dissemination contributes to vascular inflammation, atherogenesis, and adverse cardiac remodeling. This review critically evaluates the mechanistic pathways and clinical evidence connecting Fusobacterium nucleatum to these major disorders and highlights potential therapeutic strategies aimed at reducing its pathogenic burden.

Fusobacterium nucleatum is a Gram-negative anaerobe that occupies a central ecological niche in oral biofilms but has emerged as a trans-compartmental pathogen implicated in gastrointestinal and cardiovascular diseases. In inflammatory bowel diseases, Fusobacterium nucleatum adheres to the intestinal epithelium via adhesins such as FadA, disrupts tight junctions, and induces Toll-like receptor–mediated inflammatory cascades, amplifying epithelial permeability and sustaining mucosal inflammation. In colorectal cancer, Fusobacterium nucleatum promotes carcinogenesis through multiple mechanisms, including β-catenin activation, modulation of oncogenic microRNAs, and immune evasion via Fap2–TIGIT signaling, while also fostering a pro-inflammatory and immunosuppressive tumor microenvironment. Its enrichment correlates with advanced tumor stage, chemoresistance, and poor prognosis, underscoring its potential as a biomarker and therapeutic target. Beyond the gut, Fusobacterium nucleatum has been detected in atherosclerotic plaques and endocardial tissues, where it contributes to endothelial dysfunction, foam cell formation, oxidative stress, and plaque instability, thereby linking chronic oral infection with cardiovascular risk. Collectively, evidence suggests that Fusobacterium nucleatum acts as a pathophysiological connector across IBD, CRC, and CVD through conserved mechanisms of adhesion, immune modulation, and inflammation. Understanding these processes provides opportunities for innovative interventions, ranging from targeted antimicrobials and host-directed therapies to dietary and microbiome-based strategies, aimed at mitigating the systemic burden of this organism and improving clinical outcomes across multiple diseases.