Arja M. Kullaa

Objectives: Oral Potential Malignant Lesions (OPMDs), including oral leukoplakia (OLK) and lichen planus (OLP), as well as Oral Squamous Cell Carcinoma (OSCC) are influenced by oral dysbiosis and might represent a disease continuum. Our hypothesis was that the oral salivary metabolomic reflects the association of those diseases. Hence, we aimed to study and compare salivary metabolites and metabolic pathways in OPMDs and OSCC. Material and methods: Unstimulated saliva samples were collected from 60 participants: OLK ( n = 15), OLP ( n = 15), OSCC ( n = 15), and healthy controls (HCs; n = 15). Metabolites were quantified using NMR spectroscopy, and pathway analyses were performed with MetaboAnalyst 6.0. Results: Four metabolites (acetate, taurine, pyruvate, methylamine) were elevated, while proline was consistently decreased in all disease groups relative to HCs. Four key pathways were altered: pyruvate metabolism (in all disease groups), glutamate metabolism (in OLK and OSCC), taurine and hypotaurine metabolism (in OLP and OLK), and the glucose–alanine cycle. OLK shared more metabolic features with OSCC than with OLP. Conclusions: Salivary metabolomic profiling reveals distinct metabolic alterations across OPMDs and OSCC, supporting their potential continuum and reflecting disease-related biochemical reprogramming. These findings highlight salivary metabolomics as a promising, non-invasive tool for understanding pathogenesis and for future development of biomarkers. Clinical relevance: Divergent metabolic pathways in OLP and OLK may relate to their different pathogenesis and malignant transformation risks. Improved understanding of these pathways may support early diagnostics and targeted therapeutic strategies.

Head and neck cancer (HNC) affects numerous patients and is one of the most common cancers in the world. The treatment modalities for HNC have developed, but the mortality rate still remains relati...

Objectives Oral toxicities affect a high proportion of head and neck cancer (HNC) patients receiving radiotherapy, lacking reliable predictive biomarkers for incidence and severity. We investigated salivary metabolites and metabolic pathways as non-invasive predictors of radiotherapy-induced oral mucositis (OM) and candidiasis. Material and methods HNC patients undergoing radiotherapy were prospectively studied. Saliva samples of 45 HNC patients and 30 controls were analysed using NMR spectroscopy, and patients were assessed for oral complications during treatment. Results Significant metabolite differences were identified between patients with and without complications. An increased concentration of lactate (p < 0.000), and a reduced concentration of formate (p = 0.018) and pyruvate (p = 0.045), was found in HNC patients at risk for OM during RT. Comparison of salivary metabolites between patients at risk or not risk for candidiasis presented increases in acetate (p = 0.005), alanine (p = 0.009), proline (p = 0.002), tyrosine (p < 0.000), trimethylamine (p = 0.007) and fucose (p < 0.000), whereas the level of citrate (p = 0.008) was decreased. Of the metabolic pathways, glucose-alanine cycle and thyroid hormone synthesis, were significantly different in patients at risk for candidiasis. Conclusions Salivary metabolomics is a promising predictive tool for radiotherapy-induced oral complications, potentially enabling early intervention and personalized supportive care. Clinical relevance Elevated level of salivary lactate seems to predict the development of OM, while fucosis was a sign of candidiasis. Multicentre validation studies are needed for its clinical implementation.

This study aims to provide a new insight into the oral mucosal defense, and to investigate the oral microbial attachment to the oral mucosa. A total of 68 oral mucosal samples were prepared for light microscopy, immunohistochemistry (IHC), and both scanning and transmission electron microscopy. Tissue samples were IHC stained for transmembrane mucin 1 (tMUC1), which was also examined with immuno-scanning electron microscopy (iSEM). The scanning electron microscopy (SEM) images were procured to analyze the attachment of microbes on different parts of the oral mucosa. The IHC for tMUC1 presented its localization in the apical portion of the superficial surface of non-keratinized epithelial cells, whereas no such expression was observed in keratinized epithelium. In SEM images, the microplicae (MPL) structure organized in non-keratinized epithelial cells, and iSEM showed tMUC1 localized at the tips of MPLs. Microbial attachment was low in the areas showing tMUC1-MPL-structures, whereas more abundant in the areas that lack tMUC1 attachment with MPL. The superficial MPL and the attachment of tMUC1 form a complex that functionally prevents the attachment of microbes. The iSEM confirms that tMUC1 is a polarity protein, which generates the apical MPL structure in oral epithelial surface cells and together provides protection against microbial colonization and invasion.

Mucins are a family of heavily glycosylated proteins that form the main organic component of the oral mucosal barrier complex. Transmembrane mucin 1 (tMUC1) is anchored at the superficial epithelial surface to provide a protective function. The interaction of tMUC1 with oral microbes provides nutrients and physicochemical protection, promotes adhesion, and increases the microbe residence time in the oral cavity. Mucin-degrading microorganisms in the consortia also offer some advantages to oral microbes. The high molecular weight of mucin glycoproteins is hard to study because of their size, complexity, and heterogeneity. This review discusses how mucin facilitates oral microbiome colonization and how mucin–microbial interactions influence the development of oral cancer, mainly oral squamous cell carcinoma.

Background Although there have been significant advancements in reducing the burden of cardiovascular disease (CVD) by modifying traditional CVD risk factors, substantial risks persist, particularly among male subjects who exhibit heightened susceptibility to atherosclerosis. In this context, we aim to study the link between oral microbiome and carotid intima media thickness (cIMT). Methods The Northern Finland Birth Cohort of 1966 (mean age 46 years, n = 869) underwent an extensive health examination, including the measurement of cIMT. The oral microbiome was also investigated using high-throughput 16S rRNA gene sequencing. Results Here we show that oral microbiome diversity links with atherosclerosis risk factors, namely smoking, glycemic balance, low-grade inflammation, and periodontitis. After excluding CVD-influencing factors (n = 339), oral microbiome genera (p = 0.030), Shannon index (p = 0.001), β-diversity Bray–Curtis (p < 0.001), and Jaccard (p < 0.001) are associated with cIMT in males, but not in the female sub-cohort. Furthermore, in the male sub-cohort (n = 131), the genera Prevotella, Megasphaera, and Veillonella associate positively with cIMT, while Absconditabacteria, Capnocytophaga, Gemella, Fusobacterium, Neisseria, Aggregatibacter, Tannerella, Treponema, Cardiobacterium, and Bacteroidales associate inversely with cIMT. We examine the involvement of serum total immunoglobulins and antibodies to phosphorylcholine (PCho) and malondialdehyde-acetaldehyde LDL (MAA-LDL) with cIMT. Subjects with high cIMT have lower levels of serum total IgA (p = 0.009), IgA to PCho (p = 0.017), and IgG to PCho (p = 0.008). The relative abundance of cIMT-associated genera correlates with serum IgA antibodies. Conclusions This middle-aged birth cohort study shows that male oral microbiome diversity links to cIMT, suggesting a potential sex-specific interaction between the oral microbiome and atherosclerosis.

Introduction: This longitudinal study assessed the salivary metabolic profile in patients with head and neck cancer (HNC) treated with radiotherapy (RT). This study aims to investigate salivary metabolites and biological oral pathways induced by RT. Methods: Clinical data and unstimulated whole-mouth saliva (USWMS) were obtained from 45 HNC patients before, during, and one week after the RT. Data was also collected from 30 healthy controls. NMR spectroscopy identified and quantified 24 metabolites. Spearman’s rank correlation analysis and pathway enrichment analysis (MetaboAnalyst 6.0) was performed to check the effect of cancer therapy on the correlation and pathways of different salivary metabolites. Results: Of 24 metabolites identified, 17 salivary metabolites showed a consistent decrease in the concentration during and after treatment of HNC patients. The metabolite proline decreased, whereas fucose and 1,2-Propanediol were increased in the saliva causing altered redox balance and abnormal fucosylation in HNC patients compared to controls. Spearman correlation analysis indicated changes between pyruvate and some other metabolites, including alanine, trimethylamine, choline, taurine, and succinate, during RT. Five pathways (Pyruvate metabolism; Glycolysis / Gluconeogenesis; Glycine, serine, and threonine metabolism; Glyoxylate and dicarboxylate metabolism; and Alanine, aspartate and glutamate metabolism) are affected, demonstrating the metabolic dysregulation due to RT. The pyruvate metabolism was overpresented with the high Pathway Impact score. Conclusion: Salivary metabolomics analysis revealed significant alterations in the metabolic profile of HNC patients undergoing RT, providing valuable insights into treatment-induced oral pathobiological changes. Alterations in salivary pathways during RT suggest disturbances in redox homeostasis, oxidative stress, and inflammation. The ability to monitor salivary metabolites and pathways non-invasively holds promise to personalized medicine in HNC treatment by enabling early detection of treatment-related toxicities, monitoring treatment response, and tailoring interventions to patient needs.

Background: The association between cognitive neurodegenerative disease and oral diseases has been under great interest recently. Several studies have suggested a connection between periodontitis and Alzheimer's disease (AD) or other neurodegenerative disorders. Objective: This study aimed to review the potential mechanisms between oral diseases and neurodegenerative diseases. Methods: The study was executed as a literature review of English-language publications from 2018–2022. The databases used for the search were PubMed, Cochrane, Scopus, and Web of Science. The search phrases used were “ neurodegenerative diseases ” AND “ oral health ” and “ neurodegenerative diseases ” AND “ oral diseases .” Results: The linkage between the two disease groups was observed in several distinct publications and several potential mechanisms were found. The link between periodontitis and AD proved to be the most significant. The effect was accentuated in elderly people where individuals possessed also other risk factors for neurodegenerative diseases and had generally worse oral health conditions. Conclusions: Oral diseases may be risks for neurodegenerative changes along many different pathways. Good oral health should be acknowledged as a potential preventative or risk-reducing act against neurodegenerative diseases.

Candida albicans are ubiquitous fungal organisms that colonize the oral cavity of healthy individuals without causing disease. C. albicans is an opportunistic microorganism with several virulent factors that influence the inflammatory process and allow it to invade tissues, evade host defense mechanisms, and release toxins, facilitating proliferation and degradation. At present, increasing emphasis is placed on polymicrobial interactions between C. albicans and various bacterial pathogens. Such interaction is mutually beneficial for both parties: it is competitive and antagonistic. Their complex interaction and colonization in the oral cavity serve as the basis for several oral diseases. The dispersion of C. albicans in saliva and the systemic circulation is noted in association with other bacterial populations, suggesting their virulence in causing disease. Hence, it is necessary to understand fungal–bacterial interactions for early detection and the development of novel therapeutic strategies to treat oral diseases. In this paper, we review the mutualistic interaction of C. albicans in oral biofilm formation and polymicrobial interactions in oral diseases. In addition, C. albicans virulence in causing biofilm-related oral diseases and its presence in saliva are discussed.