The oral cavity hosts over 700 different microbial species that produce a rich reservoir of bioactive metabolites critical to oral health maintenance. Over the last two decades, new insights into the oral microbiome and its importance in health and disease have emerged mainly due to the discovery of new oral microbial species using next-generation sequencing (NGS). This advancement has revolutionized the documentation of unique microbial profiles associated with different niches and health/disease states within the oral cavity and the relation of the oral bacteria to systemic diseases. However, less work has been done to identify and characterize the unique oral microbial metabolites that play critical roles in maintaining equilibrium between the various oral microbial species and their human hosts. This article discusses the most significant microbial metabolites produced by these diverse communities of oral bacteria that can either foster health or contribute to disease. Finally, we shed light on how advances in genomics and genome mining can provide a high throughput platform for discovering novel bioactive metabolites derived from the human oral microbiome to tackle emerging human infections and systemic diseases.

Periodontitis (PD) is increasingly considered to interact with and promote a number of inflammatory diseases, including cancer. In the case of oral squamous cell carcinoma (OSCC) the local inflammatory response associated with PD is capable of triggering altered cellular events that can promote cancer cell invasion and proliferation of existing primary oral carcinomas as well as supporting the seeding of metastatic tumor cells into the gingival tissue giving rise to secondary tumors. Both the immune and stromal components of the periodontium exhibit phenotypic alterations and functional differences during PD that result in a microenvironment that favors cancer progression. The inflammatory milieu in PD is ideal for cancer cell seeding, migration, proliferation and immune escape. Understanding the interactions governing this attenuated anti-tumor immune response is vital to unveil unexplored preventive or therapeutic possibilities. Here we review the many commonalities between the oral-inflammatory microenvironment in PD and oral-inflammatory responses that are associated with OSCC progression, and how these conditions can act to promote and sustain the hallmarks of cancer.

Neutrophils, also known as polymorphonuclear leukocytes (PMNs), form a significant component of the innate host response, and the consequence of the interaction between the oral microbiota and PMNs is a crucial determinant of oral health status. The impact of radiation therapy (RT) for head and neck tumour (HNT) treatment on the oral innate immune system, neutrophils in particular, and the oral microbiome has not been thoroughly investigated. Therefore, the objective of this study was to characterize RT-mediated changes in oral neutrophils (oPMNs) and the oral microbiome in patients undergoing RT to treat HNTs. Oral rinse samples were collected prior to, during and post-RT from HNT patients receiving RT at Dental Oncology at Princess Margaret Cancer Centre. The oPMNs counts and activation states were analysed using flow cytometry, and the oral microbiome was analysed using 16S rRNA gene sequencing. Statistically significant (p < 0.05) drops in oPMN counts and the activation states of the CD11b, CD16, CD18, CD64 and H3Cit markers from pre-RT to post-RT were observed. Moreover, exposure to RT caused a significant reduction in the relative abundance of commensal Gram-negative bacteria and increased the commensal Gram-positive microbes. Ionizing radiation for the treatment of HNTs simultaneously decreased the recruitment of oPMNs into the oral cavity and suppressed their activation state. The oral microbiome composition post-RT was altered significantly due to RT which may favour the colonization of specific microbial communities unfavourable for the long-term development of a balanced oral microbiome.

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Background Bloodstream infections (BSI) are the most common infectious complications in patients receiving allogeneic hematopoietic stem-cell transplants (allo-HSCT). Polymorphonuclear neutrophils (PMN) are quantified to monitor the susceptibility to BSIs, however, their degree of activation is not. We previously identified a population of primed PMNs (pPMN) with distinct markers of activation representing ∼10% of PMNs in the circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMN rather than strictly PMN counts. Methods In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day five post-transplant to categorize patients into a high- or a low-pPMN group (&gt; or &lt;10% pPMNs). These groups were then used as a predictor of BSIs. Results A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSI compared to patients in the high-pPMN group with an odds ratio of 6.5 (95% CI= 2.110-25.07, P= 0.002). Conclusion In patients receiving an allo-HSCT, having less than 10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients.