Microstructural changes in the irradiated and osteoradionecrotic bone: a SEM study.

Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls (p < .05). The number of HCs decreased in irradiated and ORN bone compared to the control group. However, this was statistically not significant. The deleterious effect of radiation continues gradually altering the bone quality, structure, cellularity, and vascularity in the long term (>5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.

Salivary metabolomics in patients with oral lichen planus: a preliminary study based on NMR spectroscopy.

OBJECTIVES: The present preliminary study aimed to investigate the salivary metabolic profile in patients with asymptomatic oral lichen planus (OLP) using nuclear magnetic resonance (NMR) spectroscopy. MATERIAL AND METHODS: Stimulated whole mouth saliva (SWMS) samples were collected from 15 reticular OLP female patients and 15 from age- and sex-matched controls (HCs). A total of 23 metabolites were identified and quantified. Mann-Whitney's U test was used to compare the determined concentration salivary metabolite concentrations between OLP patients and the healthy controls. RESULTS: The concentration of acetate, methylamine, and pyruvate was elevated, whereas the concentration of tyrosine was decreased in the saliva of OLP patients compared with HCs. To identify a combination of metabolites, multivariate discrimination function analysis (DFA) was conducted. DFA analysis have shown that the most powerful discrimination between the groups was achieved when methylamine and tyrosine were considered as combined biomarkers. CONCLUSIONS: Salivary tyrosine was of particular interest and a promising finding for the screening of OLP and its progression. Further longitudinal studies are required to establish it as a reliable salivary biomarker in OLP. CLINICAL RELEVANCE: The salivary metabolic profiling can describe the pathologic characteristics of OLP on non-invasive saliva samples and NMR analysis. Salivary metabolites provide details to considered early detectors and to impact oral health of OLP patients.

Molecular Quantity Variations in Human-Mandibular-Bone Osteoid.

Osteoid is a layer of new-formed bone that is deposited on the bone border during the process of new bone formation. This deposition process is crucial for bone tissue, and flaws in it can lead to bone diseases. Certain bone diseases, i.e. medication related osteonecrosis, are overexpressed in mandibular bone. Because mandibular bone presents different properties than other bone types, the data concerning osteoid formation in other bones are inapplicable for human-mandibular bone. Previously, the molecular distribution of other bone types has been presented using Fourier-transform infrared (FTIR) spectroscopy. However, the spatial distribution of molecular components of healthy-human-mandibular-bone osteoid in relation to histologic landmarks has not been previously presented and needs to be studied in order to understand diseases that occur human-mandibular bone. This study presents for the first time the variation in molecular distribution inside healthy-human-mandibular-bone osteoid by juxtaposing FTIR data with its corresponding histologic image obtained by autofluorescence imaging of its same bone section. During new bone formation, bone-forming cells produce an osteoid constituted primarily of type I collagen. It was observed that in mandibular bone, the collagen type I increases from the osteoblast line with the distance from the osteoblasts, indicating progressive accumulation of collagen during osteoid formation. Only later inside the collagen matrix, the osteoid starts to mineralize. When the mineralization starts, the collagen accumulation diminishes whereas the collagen maturation still continues. This chemical-apposition process in healthy mandibular bone will be used in future as a reference to understand different pathologic conditions that occur in human-mandibular bone.

Effects of irradiation in the mandibular bone loaded with dental implants. An experimental study with a canine model.

Radiation therapy may compromise the quality of bone around dental implants, and its ability to regenerate, remodel, and revascularize. This study aimed to describe the irradiation effect on the bone microstructure of the mandible using dental implants in a canine model. Five beagle dogs were exposed to 40 Gy fractionated radiation. In total, 20 dental implants were inserted, two in the irradiated and two in the non-irradiated side. The mandible bone blocks were subjected to 3D micro-computed tomography (µCT) imaging, later evaluated histomorphometrically by light microscopy and scanning electron microscopy. Alterations in irradiated bone were observed under µCT imaging showing an increased anisotropy, porosity, and pore volume. Bone surface-to-bone volume decreased. The bone to implant contact index was significantly reduced in the irradiated bone (75.6% ± 5.8%) as compared to the non-irradiated bone (85.1% ± 6.8%). In the irradiated mandible, osteocytes with their filopodial processes, the bone beneath the periosteum, and subperiosteal veins showed structural differences but were not significant, whereas the diameter of Haversian canals were smaller statistical significant as compared to the control side. The study highlights that radiation dosage of fractioned 40 Gy causes alterations in the alveolar bone microstructure with compatible osseointegration and clinically stable dental implants.

Metabolome of canine and human saliva: a non-targeted metabolomics study.

INTRODUCTION: Saliva metabolites are suggested to reflect the health status of an individual in humans. The same could be true with the dog (Canis lupus familiaris), an important animal model of human disease, but its saliva metabolome is unknown. As a non-invasive sample, canine saliva could offer a new alternative material for research to reveal molecular mechanisms of different (patho)physiological stages, and for veterinary medicine to monitor dogs' health trajectories. OBJECTIVES: To investigate and characterize the metabolite composition of dog and human saliva in a non-targeted manner. METHODS: Stimulated saliva was collected from 13 privately-owned dogs and from 14 human individuals. We used a non-targeted ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) method to measure metabolite profiles from saliva samples. RESULTS: We identified and classified a total of 211 endogenous and exogenous salivary metabolites. The compounds included amino acids, amino acid derivatives, biogenic amines, nucleic acid subunits, lipids, organic acids, small peptides as well as other metabolites, like metabolic waste molecules and other chemicals. Our results reveal a distinct metabolite profile of dog and human saliva as 25 lipid compounds were identified only in canine saliva and eight dipeptides only in human saliva. In addition, we observed large variation in ion abundance within and between the identified saliva metabolites in dog and human. CONCLUSION: The results suggest that non-targeted metabolomics approach utilizing UHPLC-qTOF-MS can detect a wide range of small compounds in dog and human saliva with partially overlapping metabolite composition. The identified metabolites indicate that canine saliva is potentially a versatile material for the discovery of biomarkers for dog welfare. However, this profile is not complete, and dog saliva needs to be investigated in the future with other analytical platforms to characterize the whole canine saliva metabolome. Furthermore, the detailed comparison of human and dog saliva composition needs to be conducted with harmonized study design.

Prevalence of oral mucosal normal variations and lesions in a middle-aged population: a Northern Finland Birth Cohort 1966 study.

BACKGROUND: In this cross-sectional study we investigated the oral mucosal changes in a middle-aged Finnish population. We analyzed the prevalence of potentially malignant disorders and the influence of smoking, snuff and alcohol use on the mucosal changes. METHODS: Of the 12,068 members of the NFBC 1966, a total of 1961 participants (16.2%) constituted the study population. Mucosal changes were diagnosed and photographed by seven general dentists, and two specialists re-analyzed all the diagnoses based on the documentation Cross-tabulation with Chi-square tests and logistic regression analysis were used to analyze the data. RESULTS: Of the participants, 10.5% had some mucosal changes, of which 81.8% were diagnosed as oral mucosal lesions (OML) and 18.2% as normal variations. Of the normal variations, the most common were Fordyce granules (1.2%), fissured tongue (1.1%) and geographic tongue (0.9%). The most common OMLs were white lesions (6.5%), of which oral lichen planus (OLP) and lichenoid reactions (OLR), grouped as oral lichenoid diseases, were present in 3.5%, males more often (3.8% vs. 3.1%). OLP was found in 1.5% of all participants, females more often (1.8% vs. 1.2%), while OLR was more common in males (2.7% vs. 1.3%). Leukoplakia was identified in 0.5% of the population; twice more often in males (0.6% vs. 0.3%). Erythroplakia was not found. Current smokers had higher risk for oral mucosal changes than former or non-smokers (OR 3.0, 95% CI 2.11-4.28), and snuff, used occasionally or regularly, also raised the risk (OR 2.6, 95% CI 1.48-4.70). CONCLUSIONS: In the middle-aged northern Finland population, 4% of OMLs were potentially malignant disorders, including OLR (2%), OLP (1.5%) and leukoplakia (0.5%). In particular, smoking and snuff use increased the risk for having any oral mucosa changes.

Optical implementation of partially negative filters using a spectrally tunable light source, and its application to contrast enhanced oral and dental imaging.

In optical imaging, optical filters can be used to enhance the visibility of features-of-interest and thus aid in visualization. Optical filter design based on hyperspectral imaging employs various statistical methods to find an optimal design. Some methods, like principal component analysis, produce vectors that can be interpreted as filters that have a partially negative transmission spectrum. These filters, however, are not directly implementable optically. Earlier implementations of partially negative filters have concentrated on spectral reconstruction. Here we show a novel method for implementing partially negative optical filters for contrast-enhancement purposes in imaging applications. We describe the method and its requirements, and show its feasibility with color chart and dental imaging examples. The results are promising: visual comparison of computational color chart render and optical measurement show matching images, and visual inspection of dental images show increased contrast.

Localization of transmembrane mucin MUC1 on the apical surface of oral mucosal cells.

The purpose of the present study was to demonstrate the localization of transmembrane mucin MUC1 on the outer layer of oral mucosal cells and the involvement of apical cell surface microplicae (MPL) in bioadhesion of MUC1. Tissue samples of six healthy subjects were obtained. First, the presence of MUC1 was examined with an immunohistochemical method using a monoclonal MUC1 antigen called HFMG1. Second, the localization of MUC1 was examined with immuno-scanning electron microscopy. Immunohistochemically, high intense staining for MUC1 (antigen HFMG1) was detected in the epithelial superficial layers. In the superficial layer, intense MUC1 expression was seen predominantly on the apical cell surface. On the apical epithelial cells, MUC1 was associated predominantly with MPL towards the oral cavity. The novelty of the results of the present study is that MPL serves a harbor of MUC1 in superficial epithelial cells towards the oral cavity. It is speculated that the transmembrane MUC1 is one component of the "oral mucosal barrier complex" representing a signaling pathway between saliva and mucosal cells.Abbreviations: MUC1: mucin1; MAM: membrane-anchored mucin; OMBC: oral mucosal barrier complex; LM: light microscopy; TEM: transmission electron microscopy; SEM: scanning electron microscopy; iSEM: immuno-scanning electron microscopy; MPL: microplicae.

Alveolar bone remodeling after tooth extraction in irradiated mandible: An experimental study with canine model.

OBJECTIVES: The aim of the present study is to investigate the morphological and cellular changes in dental extraction socket that has been irradiated after the tooth extraction and to describe morphological characteristics of the osteocytes and osteocyte-lacunar-canalicular network (LCN) by scanning electron microscopy (SEM). MATERIAL AND METHODS: Five beagle dogs aged 1-2 years were used in this study. One side of each mandible was irradiated in two sessions and the other side of mandible (non-irradiated) served as a control. The mandible bone blocks were processed by bulk staining en bloc in basic fuchsin and the specimens were embedded routinely in polymethyl methacrylate resin without preliminary decalcification. All blocks were subjected to micro-CT imaging, after that the specimens were prepared for light microscopy and SEM. RESULTS: Alterations in bone macrostructure are minimal in irradiated bone, but the changes in LCN are clear. In the area of the tooth extraction socket, the connections of osteocytes to the vessels and to neighboring osteocytes were not observed both in irradiated and nonirradiated bone. However, osteoclasts were located in the bone surface entering inside to the bone between osteons. In the lamellar bone of lateral sides, a decrease in canalicular connections between osteocytes and periosteum was found in irradiated bone as compared to the non-irradiated side. CONCLUSIONS: The novelty of the present study is that radiation disrupts osteocytes and their dendrites.

Acid-etching technique of non-decalcified bone samples for visualizing osteocyte-lacuno-canalicular network using scanning electron microscope.

The aim of this study was to define the acid-etching technique for bone samples embedded in polymethyl metacrylate (PMMA) in order to visualize the osteocyte lacuno-canalicular network (LCN) for scanning electron microscopy (SEM). Human jaw bone tissue samples (N = 18) were collected from the study population consisting of patients having received dental implant surgery. After collection, the bone samples were fixed in 70% ethanol and non-decalcified samples embedded routinely into polymethyl metacrylate (PMMA). The PMMA embedded specimens were acid-etched in either 9 or 37% phosphoric acid (PA) and prepared for SEM for further analysis. PMMA embedded bone specimens acid-etched by 9% PA concentration accomplishes the most informative and favorable visualization of the LCN to be observed by SEM. Etching of PMMA embedded specimens is recommendable to start with 30 s or 40 s etching duration in order to find the proper etching duration for the samples examined. Visualizing osteocytes and LCN provides a tool to study bone structure that reflects changes in bone metabolism and diseases related to bone tissue. By proper etching protocol of non-decalcified and using scanning electron microscope it is possible to visualize the morphology of osteocytes and the network supporting vitality of bone tissue.

Concentric Ring Probe for Bioimpedance Spectroscopic Measurements: Design and Ex Vivo Feasibility Testing on Pork Oral Tissues.

Many oral diseases, such as oral leukoplakia and erythroplakia, which have a high potential for malignant transformations, cause abnormal structural changes in the oral mucosa. These changes are clinically assessed by visual inspection and palpation despite their poor accuracy and subjective nature. We hypothesized that non-invasive bioimpedance spectroscopy (BIS) might be a viable option to improve the diagnostics of potentially malignant lesions. In this study, we aimed to design and optimize the measurement setup and to conduct feasibility testing on pork oral tissues. The contact pressure between a custom-made concentric ring probe and tissue was experimentally optimized. The effects of loading time and inter-electrode spacing on BIS spectra were also clarified. Tissue differentiation testing was performed for ex vivo pork oral tissues including palatinum, buccal mucosa, fat, and muscle tissue samples. We observed that the most reproducible results were obtained by using a loading weight of 200 g and a fixed time period under press, which was necessary to allow meaningful quantitative comparison. All studied tissues showed their own unique spectra, accompanied by significant differences in both impedance magnitude and phase (p ≤ 0.014, Kruskal-Wallis test). BIS shows promise, and further studies are warranted to clarify its potential to detect specific pathological tissue alterations.

Radiation-induced changes in the microstructure of epithelial cells of the oral mucosa: A comparative light and electron microscopic study.

OBJECTIVES: The microplicae is a typical structure of the epithelial cell surface of the oral mucosa. The cell surface is potentially of great significance, as it provides the underlying basis for the protective function of the salivary pellicle. The aim of this study was to investigate whether radiation therapy affects the surface morphology of the superficial cells of the human oral mucosa in patients who have received radiotherapy for oral cancer. MATERIAL AND METHODS: Oral mucosal tissue samples from 91 patients were collected during dental implant surgery or ablative surgery. Study group 1 consisted of 28 patients who underwent dental implant surgery after radiotherapy. Group 2 consisted of five patients who developed osteoradionecrosis. Group 3 consisted of eight oral cancer patients without radiotherapy. Group 4 consisted of 50 clinically healthy subjects as controls. The samples were studied with scanning electron microscopy and compared with both light and transmission electron micrographs. RESULTS: Radiation therapy (RT) induces breakage and destruction in the microplicae morphology and declines the density of the microplicae surface structures. In some of the irradiated cells, the microplicae were completely vanished, especially in patients who developed osteoradionecrosis. In non-irradiated tissue, the microplicae of the superficial epithelial cells were intact in all cases. CONCLUSION: Scanning electron microscopy, in contrast to light microscopy, appears to be a useful tool to reveal the condition of superficial oral mucosal cells. In respect of the possible pathogenesis of osteoradionecrosis, the radiation-induced damage of the microplicae and its influence on the mucosal salivary pellicle is discussed.

Cross-reactive saliva IgA antibodies to oxidized LDL and periodontal pathogens in humans.

AIM: Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and are highly immunogenic and proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were characterized and their cross-reactivity was evaluated. MATERIALS AND METHODS: Resting and stimulated saliva samples were collected from 36 healthy adults (mean age 26 years). Saliva IgA, IgG and IgM autoantibody levels to copper oxidized LDL (CuOx-LDL) and malondialdehyde acetaldehyde-modified LDL (MAA-LDL) were determined with chemiluminescence immunoassay. RESULTS: Saliva IgA and IgG antibodies binding to MAA-LDL and CuOx-LDL were detected in all samples and they were associated with the saliva levels of IgA and IgG to P. gingivalis and A. actinomycetemcomitans. Competitive immunoassay showed that saliva antibodies to MAA-LDL cross-reacted specifically with P. gingivalis. The autoantibody levels to oxLDL in saliva were not associated with the autoantibody levels to oxLDL in plasma or with saliva apolipoprotein B 100 levels. CONCLUSIONS: Saliva contains IgA and IgG binding to oxLDL, which showed cross-reactive properties with the periodontal pathogens Porphyromonas gingivalis (P.g). The data suggest that secretory IgA to P.g may participate in immune reactions involved in LDL oxidation through molecular mimicry.

Altered expression of hyaluronan, HAS1-2, and HYAL1-2 in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated mucosal disease of unclear etiology and of unresolved pathogenesis. Hyaluronan (HA) is an extracellular matrix glycosaminoglycan involved in inflammation and tumor progression. However, its presence in OLP has not been reported. We therefore aimed to study the immunohistochemical expression of HA, its receptor CD44, hyaluronan synthases (HAS1-3), and hyaluronidases (HYAL1-2) in OLP. METHODS: The presence of HA, CD44, HAS1-3, and HYAL1-2 was studied by immunohistochemical methods in 55 OLP and 23 control oral mucosal specimens (CTR). The localization, intensity, and differences of the epithelial expression between OLP and CTRs were analyzed. RESULTS: HA and CD44 were found on cell membranes in the epithelial basal and intermediate layers in CTR and OLP specimens. The HA staining intensity was stronger in the basal layer of the epithelium in OLP than in CTRs (P < 0.001). HAS1 (P = 0.001) and HAS2 (P < 0.001) showed stronger staining in the basal and weaker staining in the superficial (P < 0.001) epithelial layers in OLP than in CTRs. The immunostaining of HAS3 was low in both OLP and CTRs. Positive HYAL1 and HYAL2 staining were mainly found in the basal and intermediate epithelial layers, and their intensities were significantly increased in OLP, except HYAL 2 in the intermediate epithelial layer. CONCLUSIONS: HA, HAS1-2, and HYAL1-2 have altered expression in OLP compared to CTRs and may therefore have a role in OLP pathogenesis.

Surface morphology of superficial cells in irradiated oral mucosa: an experimental study in beagle dog.

OBJECTIVES: The aim of the present study is to investigate if radiation induces changes in the superficial cells of the oral mucosa and secondly to describe morphological characteristics of the cell surface structure by scanning electron microscopy (SEM). MATERIALS AND METHODS: Ten beagle dogs aged 1-2 years were used in this study. One side of each mandible was irradiated in two sessions, each lasting 1 week. The total dosage was 40 Gy (Group A; 5 dogs) and 50 Gy (Group B; 5 dogs), in five fractions of 4 Gy. The other side of mandible (non-irradiated) served as a control. The specimen was harvested with a scalpel from the alveolar mucosa of the irradiated area 1 year after irradiation and studied with SEM. RESULTS: In the control side, the surface structure of the cell contains straight parallel or branched microplicae (MPL), which were equally spaced over the cell surfaces. Discontinuous and short MPL were typical cell structure of irradiated mucosa. In 50 Gy group, the surface structure of epithelial cell was pitted and the cell boundaries were thick. CONCLUSIONS: The novelty of the present study is that radiation disrupts superficial cells of the oral mucosa. The role of the MPL structure of the superficial cells in mucositis development is discussed.

Microstructure of the superficial epithelial cells of the human oral mucosa.

BACKGROUND: The apical cell membrane of the oral mucosa adjacent to the saliva interface is thrown into membrane folds, termed microplicae (MPL) with variation in morphology. The present study classifies morphological changes undergone by MPL into qualitative and quantitative categories. MATERIAL AND METHODS: Oral mucosal specimens were obtained from 32 healthy patients. Half of each specimen was prepared routinely for light microscopy, and the other part for scanning and transmission electron microscopy. Different measurements of cell structure were presented: the density of MPL, the width and height of MPL, the width of furrows between two adjacent MPL and the distance of the centre of MPL. Morphometric measurements were obtained using a semiautomatic ImageJ analysis software (W Rasband, National Institutes of Health, Bethesda, MD). RESULTS: Parallel and branching MPL was common observation in the area of lining mucosa and in the tongue between the filiform papillae. The density of MPL was higher in the cells of the buccal mucosa than in the cells of the tongue, 43.69 + 11.43% and 31.68 + 10.32%, respectively. The difference was significant (p < 0.001). The width of MPL was 0.16 µm in cells of the buccal mucosa and 0.12 µm in cells of the tongue. CONCLUSIONS: Our findings support the idea that MPL structure is a determining factor for the functionality of the oral epithelium since the values of the MPL were kept relatively stable. The role of MPL structure of the oral mucosal cells is discussed.

Microstructure of oral epithelial cells as an underlying basis for salivary mucosal pellicle.

BACKGROUND: Salivary mucosal pellicle forms the structural basis of the local innate immune defense mechanism of the oral mucosa. At the surface of the oral mucosa, the apical cell membrane adjacent to the saliva interface contains short membrane folds, termed microplicae (MPL). This MPL structure of oral epithelial cells and its function as a basis to the salivary mucosal pellicle is unclear. In this preliminary study, we describe the ultrastructural morphology of cell membrane of superficial cells of the oral mucosa and study the membrane-associated mucins (MAMs), MUC1 and MUC4, with immunohistological methods. MATERIALS AND METHODS: Oral mucosal specimens were obtained from six healthy patients. Half of each specimen was prepared routinely for light microscopy, and the other part for scanning and transmission electron microscopy. The presence of MUC1 and MUC4 were studied by immunohistochemical methods in oral mucosal specimens. RESULTS: Morphologically, the cell membrane of MPL is partly discontinuous and membrane-associated molecules extrude from the cell membrane. MUC1 expression was detected in the superficial part of the buccal epithelium, while MUC4 had no expression in the oral squamous epithelium. CONCLUSIONS: The novel of this study is that the membrane-tethered molecules seem to occur onto the cell membrane of the superficial epithelial cells of the oral mucosa. Furthermore, the stratified squamous epithelium of the buccal mucosa produces MUC1 for the surface-saliva pellicle interface. The interaction between MPL structure, MUC1 mucin, and salivary mucosal pellicle is discussed.

Salivary Metabolites Produced by Oral Microbes in Oral Diseases and Oral Squamous Cell Carcinoma: A Review.

In recent years, salivary metabolome studies have provided new biological information and salivary biomarkers to diagnose different diseases at early stages. The saliva in the oral cavity is influenced by many factors that are reflected in the salivary metabolite profile. Oral microbes can alter the salivary metabolite profile and may express oral inflammation or oral diseases. The released microbial metabolites in the saliva represent the altered biochemical pathways in the oral cavity. This review highlights the oral microbial profile and microbial metabolites released in saliva and its use as a diagnostic biofluid for different oral diseases. The importance of salivary metabolites produced by oral microbes as risk factors for oral diseases and their possible relationship in oral carcinogenesis is discussed.

Salivary Short-chain Fatty Acids (SCFAs) Are Viable Predictors of Early Changes in Systemic Health.

Short-chain fatty acids (SCFAs) are the metabolites identified in both the oral cavity and the gut. They play an important role in the triggering, development and progression of systemic diseases. SCFAs can alter the gut microbial components, intestinal epithelium and host immune system, and are also associated with cancer incidence. Salivary SCFAs, produced by the oral microbiome, are correlated with some oral diseases. The occurrence of systemic diseases associated with gut SCFAs is more clearly defined than oral SCFAs. Salivary SCFAs can enter the bloodstream directly via inflamed gingiva to cause continuous low-grade systemic inflammation. Hence, salivary SCFAs could be an indicator for the early diagnosis of systemic diseases. Furthermore, they provide a basis for understanding the oral-systemic axis driven through salivary SCFAs in the pathogenesis of several diseases.

Oral Sources of Salivary Metabolites.

The oral cavity is very diverse, wherein saliva plays an important role in maintaining oral health. The metabolism of saliva has been used to investigate oral diseases as well as general diseases, mainly to detect diagnostic biomarkers. There are many sources of salivary metabolites in the mouth. Online English language sources and the PubMed database were searched to retrieve relevant studies on oral salivary metabolites. The physiological balance of the mouth is influenced by many factors that are reflected in the salivary metabolite profile. Similarly, the dysbiosis of microbes can alter the salivary metabolite profile, which may express oral inflammation or oral diseases. This narrative review highlights the factors to be considered when examining saliva and its use as a diagnostic biofluid for different diseases. Salivary metabolites, mainly small-molecule metabolites may enter the bloodstream and cause illness elsewhere in the body. The importance of salivary metabolites produced in the oral cavity as risk factors for general diseases and their possible relationship to the body's function are also discussed.