Oral Health and Dental Management

The Role of Oral Fusobacterium nucleatum in Female Breast Cancer: A Systematic Review and Meta-Analysis

Fariah I. Gaba^* Department of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UK
^*Correspondence: Fariah I. Gaba, Department of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, UK, Email:

Received: 28-Aug-2024, Manuscript No. OHDM-24-27126; Editor assigned: 30-Aug-2024, Pre QC No. OHDM-24-27126 (PQ); Reviewed: 13-Sep-2024, QC No. OHDM-24-27126; Revised: 20-Sep-2024, Manuscript No. OHDM-24-27126 (R); Published: 27-Sep-2024, DOI: 10.35248/2247-2452.24.23.1115

Description

In 2020, a staggering 2.261,419 million females were doc- umented with confirmed breast cancer diagnoses resulting in 684,966 recorded deaths, alongside further estimations that 1 in 8 women will be diagnosed during their lifetime [1].

Oral Fusobacterium nucleatum, Periodontal Disease and Breast Cancer

The significance, functionality and understanding of the human microbiome are derived primarily from a catalogue of studies into the human gut-whereby an estimated 99% of the microbial mass has its origin. However, few studies have explored the importance of the oral microbiome. The oral cavity is a cornu- copia of microorganisms, with circa 700 identifiable bacterial species [2].

The generation of dental plaque accumulates intraorally cre- ates microbial dysbiosis activating the body’s inflammatory re- sponses thus leading to gingivitis. Prolonged periods of dental plaque accumulations initiate chronic inflammatory responses, causing periodontal disease. Approximately 45%-50% of adults over 30 years old and more than 60% of people aged over 60 years old suffer from periodontal disease [1,3]. Fusobacterium nucleatum is an imperative periodontal disease-causing virulent pathogen. Identified as one of the most common gram negative anaerobic oral microbial species, it possesses an unusual spin- dle-shape, is non-spore-forming, with appreciable contributions to dysbiotic alterations and biofilm development [4].

Numerous murine model studies have demonstrated breast can- cer progression in the presence of Fusobacterium nucleatum species with additional observance in cancerous human breast tissue. This is because the by-products of Fusobacterium nu- cleatum are adept in combining with pro-inflammatory cyto- kines (IL-1, IL-6, and IL-8) to infiltrate the systemic circula- tory system, aiding cancer progression in distant bodily sites. This highlights this oral pathogen’s prominent role in creating a proinflammatory microenvironment demonstrated in periodon- tal patients and its link to female-specific breast cancer [3,5].

The Importance of Adequate Periodontal Surgical Techniques in Preventing Female-Specific Breast Cancer Development

Minimal invasive surgery is a novel approach respecting hard and soft tissues via minimal flap reflections. It advantageous- ly reduces postoperative pain, promotes healing, and improves clinical outcomes. Modification of the single flap methodology to a more minimally invasive approach in 2007 has since creat- ed a better technique for the correction of periodontal osseous defects.

A 2013 study on minimally invasive surgical techniques re- ported nominal bone loss when compared with conventional surgeries. The single flap approach has a superfluity of advan- tages to lower the risk of periodontal disease instigating bac- teria prospectively enhancing breast cancer development via reduction of post-operative recessions, prevention of blood clot contaminations, acceleration of wound-healing, minimization of post-operative pain and allowing flap repositioning with con- comitant adherence to undetached papilla [6].

The Human Oral Microbiome Database and Metagenomics/ Meta-Transcriptomics

Over the past decade, much focus has been placed into under- standing the impact of oral microbial burdens on overall sys- temic health. In 2005, The Human Oral Microbiome Database was set up for the purpose of imparting vital data on bacterial niche typologies observed within the oral cavity. As many as 1,576 genomes and 784 different taxa have been discovered, with FN species notably being identified as one of the more common phyla [7].

However, questions remain unanswered. For example, how do microbial dysbiosis and fluctuating oral microbial compositions activate periodontal disease? And do specific microbial charac- teristics relate to other systemic diseases?

Recent emergence of meta-transcriptomics and meta-genomics has permitted high throughput analysis of microbial communi- ties, aiding understanding. Customarily, microbial recognition and detection of microbes relied heavily upon culture method- ologies, nevertheless, introduction of metagenomics involves detailed evaluations of all microbial diversities, population structures, communities, functional-relationships and their in- teractive behaviours within their respective environments [8]. Despite the technology’s positives, there are some shortcom- ings with respect to inadequate study designs and sample sizes, poor sampling methodologies and deficient follow up durations.

Possible Mechanisms of Oral Fusobacterium nucleatum in Breast Cancer Development

Extensive analysis of microbial communities in both benign and malignant growths originating from breast tissue samples of female patients, were extensively evaluated in a comparative study published in 2016. The study disclosed a direct relation- ship between breast cancer malignancies and a microbial abun- dance of Fusobacterium nucleatum species-the mechanisms of which remain unclear. In 2022, a review article examined how oral Fusobacterium nucleatum species colonised lactifer- ous ducts within breast tissue and a 2020 article illustrated the capability of FN to inhabit cancerous tumours through its cou- pling to Gal-GalNAc receptors allocated on tumour cell surface membranes. This implied that oral Fusobacterium nucleatum species could reach other Gal-GalNAc-displaying tumours with the same mechanism, augmenting haematogenous Gal-GalNAc levels thus accelerating female-specific BC pathogenesis [9,10].

Future Prospects

Despite our investigation, there is still inadequate data avail- able. Further analysis into this field with more focused assess- ment objectives would be useful, taking the following into con- sideration.

• IIF approach-“Identification-Isolation-Flag-up”. A meth-od to recognize varying subtypes of the Fusobacterium nucleatum species, observed in different sections of breast tissue samples taken from female patients with confirmed breast cancer diagnoses at different disease developmen- tal stages from least to most severe (GRADES I-IV). This would allow evaluation of the activity levels and the pro- portions of species subtype present, which would later pro- vide a clearer indication of their respective contribution to breast cancer pathogenesis.

• Consequently, the IIF approach would be duplicated and implemented on a female population presenting clinical- ly with oral inflammatory conditions (gingivitis and peri- odontitis), and again thorough analysis of Fusobacterium nucleatum subtypes would be undertaken at different dis- ease progressional stages for both conditions (mild-mod- erate-severe).

It is our firm conviction that multiomics possesses immense promise for our proposal in differentiating and understanding the relational complexities between the human microbiome and cancer predisposition. At present, the evaluation of microbiome data fabricated via multiomics methodologies is still a challenge as a consequence of unsatisfactory tool availability. In order to overcome this obstacle, supplementary well-designed Random- ized Controlled Trails (RCT’s) incorporating longer follow-up periods would assist in the validation of whether meta-genomic/meta-transcriptomic changes are feasible contributors in peri- odontal therapy personalization. This collective approach could revolutionize oral healthcare, driving a structured, informed and supportive environment for patients and clinicians-potentially saving lives.

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