Editorial: Unravelling the Role of the Oral Microbiome in Cancer

Julia S. Bruno¹Ghanyah Al-Qadami²Divya Gopinath^3,4Alexa Laheij^5,6*

• ¹Hospital Sirio Libanes, São Paulo, Brazil
• ²Health and Biosecurity (CSIRO), Canberra, Australian Capital Territory, Australia
• ³Basic Medical and Dental Sciences Department, College of Dentistry, Ajman University, Ajman, United Arab Emirates, Ajman, United Arab Emirates
• ⁴Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, Ajman, United Arab Emirates
• ⁵Department of Oral Medicine, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands, Amsterdam, Netherlands
• ⁶Department of Oral and Maxillofacial Surgery, Amsterdam UMC, VU University, Amsterdam, the Netherlands, Amsterdam, Netherlands

1.Oral squamous cell carcinomas are part of the head and neck cancer group. Their global incidence is rising, with regional variations in prevalence. The primary risk factors for oral cancer remain tobacco use and alcohol consumption, although the role of human papillomavirus is increasingly recognized [1]. Yet, the cause of cancer is multifactorial, and the development of a tumor is a multistep process. Advancements in research have brought attention to the role of the oral microbiota in tumor development. Recently, polymicrobial communities have been recognized as an emerging hallmark and enabling characteristic of cancer. Microorganisms can be involved in cancer development, malignant progression and response to therapy. They are involved in tumor-promoting inflammation and genomic instability [2]. 2.Beyond their role in cancer, the oral microbiota has been studied for its association with malignant progression and response to cancer therapy and for its link to cancer-related toxicities and life-threatening clinical outcomes. This editorial explores different aspects of the oral microbiota’s role in cancer, including its role in oral cancer development (Liang et al.), diagnostic potential (Van Dijk et al.), effects on cancer-related (oral) toxicities (Zecha et al.) as well as the advanced model systems for better understanding of their role in health and disease (Gopinath et al.).3.In oral microbiome research, ongoing debate persists over the suitability of animal models as proxies for the human microbiome, considering the inherent differences between human and rodent microbial communities. A comprehensive review by Gopinath et al. highlighted that, despite their differences from humans, rodents remain a valuable model due to their suitability for closely monitoring cancer development, cost-effectiveness, ex vivo analysis of tissue specific toxicities and practical research timelines. Further, animal models help reduce the variability typically encountered in clinical settings while enabling precise control over environmental conditions and stress factors, providing deeper insights into the role of the microbiota in cancer development and progression (Gopinath et al.). 4.To better understand lifestyle risk factors such as smoking, animal models can provide valuable insights. The toxic components of tobacco lead to tissue alterations and may impact microbial composition. In Liang et al. study, healthy control and oral cancer mice were chronically exposed to tobacco smoking. The results showed that, in the first four weeks, there was no significant change in microbial diversity. However, over more extended periods (16 weeks), microbial diversity decreased, with an increase in Firmicutes and Proteobacteria, and a reduction in Bacteroidota phyla (Liang et al.). This study highlights how the chronic use of tobacco leads to dysbiosis in the oral cavity of mice and as such contributes to cancer development. It is worth mentioning that, the development of a human oral microbiota-associated mouse model by transplanting human saliva into germ-free mice - achieving a high level of donor similarity - offers a key advancement for future studies in this field [3] (Gopinath et al.).5.The role of the oral microbiota in oral squamous cell carcinoma (OSCC) is recognized, though it remains unclear whether specific microorganisms or microbial signatures are directly linked to the disease. A scoping review by Van Dijk et al. analyzed 30 studies with 1677 subjects comparing microbial diversity between OSCC patients and healthy controls and found that Fusobacteria were significantly more abundant in OSCC patients, while Actinobacteria were more prevalent in healthy controls. Firmicutes were abundant in both groups, while Spirochaetes and Bacteroidetes showed mixed abundance patterns. Among specific species, Fusobacterium nucleatum, Porphyromonas endodontalis, and Prevotella intermedia were more abundant in OSCC patients, whereas Veillonella parvula showed varying prevalence across studies. These findings suggest that the oral microbiota could be used as a diagnostic tool for OSCC, however, further research is required to identify how best to apply this knowledge in clinical settings (Van Dijk et al.).6.During and after cancer therapy, oral toxicities are frequent, and they significantly impact patients' quality of life. The type of treatment directly influences the toxicities experienced. In head and neck cancer, patients in middle-to-late clinical stages typically undergo radiochemotherapy, which increases the risk of oral mucositis, acute and chronic hyposalivation, radiation-related caries, and osteoradionecrosis. For hematologic malignancies, hematopoietic cell transplantation involves a complex treatment regimen, including chemotherapy, immunosuppressants, and, in some cases, total body irradiation. Many of these complications have been linked to changes in the oral microbiota, either as a secondary consequence or as a potential causative factor. An updated five-phase model of oral mucositis pathophysiology supports the role of microbiota alterations as a contributing factor [4]. In line with previous studies, Zecha et al. study showed that, in chemotherapy patients, oral mucositis is associated with a lower Shannon diversity index, along with a decrease in Prevotella, Fusobacterium, Selenomonas, Actinomyces, and Leptotrichia. Further, in patients who developed neutropenic fever, the diversity of the oral microbiota was significantly lower at the onset of fever (Zecha et al.).7.Early diagnosis of oral cancer is crucial for improving treatment outcomes, survival rates, and patient quality of life. The oral microbiota offers a promising, non-invasive, and cost-effective screening tool and a potential therapeutic target, particularly for high-risk individuals. This Research Topic brings together a collection of original articles and reviews, showcasing the latest advancements in research methods and expanding our current understanding of oral microbiota dynamics in cancer patients.