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Metabolites
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Salivary Metabolomics for Oral and Systemic Diseases Volume 2
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Salivary Metabolomics for Oral and Systemic Diseases Volume 2

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Advances in Metabolomics".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 19042

Special Issue Editor

Prof. Dr. Arja Kullaa

E-Mail Website
Guest Editor
Oral Medicine, Univeristy of Eastern Finland, 1, 70210 Kuopio, Finland
Interests: oral diseases; oral cancer; salivary metabolites; metabolomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Saliva is an important biological fluid and a valuable source of biological information. Saliva contains many of the same components that can be found in blood or serum, but the components of interest tend to be at a lower concentration in saliva, and their analysis demands more sensitive techniques. Metabolomics is starting to emerge as a viable method for assessing the salivary metabolites which are generated by the process of metabolism in elucidating the pathways underlying different oral and systemic diseases. Although saliva collection is non-invasive and the handling and preparation of saliva samples for metabolomic analysis is relatively simple, very few salivary studies have been published using metabolomics technologies as compared to other biofluids. Therefore, this Special Issue, “Salivary Metabolomics for Oral and Systemic Diseases”, will be dedicated to the use of metabolomics in salivary research. Specific areas of interest for this Special Issue include, but are not limited to, analytical protocols for salivary sample preparation and analysis, as well as the identification of salivary biomarkers for oral or systemic diseases and treatment monitoring.

Prof. Dr. Arja Kullaa
Guest Editor

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Keywords

  • metabolomics
  • salivary metabolites
  • oral diseases
  • oral cancer
  • periodontal diseases
  • oral microbiome
  • systemic diseases

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Published Papers (7 papers)

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Research

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13 pages, 1795 KiB  
Article
Identification of a Biomarker Panel for Diagnosis of Early Childhood Caries Using Salivary Metabolic Profile
by Seonghye Kim, Yuri Song, Seyeon Kim, Siyeong Kim, Heesam Na, Sujin Lee, Jin Chung and Suhkmann Kim
Metabolites 2023, 13(3), 356; https://doi.org/10.3390/metabo13030356 - 27 Feb 2023
Cited by 11 | Viewed by 2131
Abstract
Several studies have demonstrated that nuclear magnetic resonance (NMR) metabolic profiles can differentiate patients with caries from healthy individuals; however, these studies only identified individual metabolites. The present study aimed to identify a salivary metabolite biomarker panel for the diagnosis of early childhood [...] Read more.
Several studies have demonstrated that nuclear magnetic resonance (NMR) metabolic profiles can differentiate patients with caries from healthy individuals; however, these studies only identified individual metabolites. The present study aimed to identify a salivary metabolite biomarker panel for the diagnosis of early childhood caries (ECC). Saliva samples from children with and without caries were analyzed using NMR spectroscopy. Multivariate and univariate analyses were performed to identify the discriminating metabolites. Selected metabolites were further evaluated and used to detect ECC. The saliva samples of children with ECC were characterized based on the increased levels of formate, glycerophosphocholine, and lactate and reduced levels of alanine, glycine, isoleucine, lysine, proline, and tyrosine. The levels of these metabolites were significantly different from those in the control in the ECC subgroup according to caries severity and correlated with the number of decayed and filled teeth or surfaces. Subsequently, an optimal salivary metabolite biomarker panel comprising formate, lactate, proline, and glycine was developed. This panel exhibited a better diagnostic performance for ECC than a single metabolite. These results demonstrate that salivary metabolic signatures can reflect oral conditions associated with dental caries, thereby emphasizing the importance of distinct salivary metabolic profiles as potential biomarkers of ECC. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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13 pages, 1569 KiB  
Article
Metabolic Profile of Whole Unstimulated Saliva in Patients with Sjögren’s Syndrome
by Giacomo Setti, Valeria Righi, Adele Mucci, Lucia Panari, Giuditta Bernardelli, Elisabetta Tarentini, Anna Gambini, Ugo Consolo, Luigi Generali, Cristina Magnoni, Marco Meleti, Gilda Sandri and Pierantonio Bellini
Metabolites 2023, 13(3), 348; https://doi.org/10.3390/metabo13030348 - 27 Feb 2023
Cited by 5 | Viewed by 2300
Abstract
Primary Sjögren’s Syndrome (pSS) is a multi-system autoimmune disease that involves the exocrine glands. Lymphocytes infiltrate the gland tissue, leading to anatomical modification and hypofunction. Even if the prognosis of pSS is favorable, quality of life is typically reduced due to the diverse [...] Read more.
Primary Sjögren’s Syndrome (pSS) is a multi-system autoimmune disease that involves the exocrine glands. Lymphocytes infiltrate the gland tissue, leading to anatomical modification and hypofunction. Even if the prognosis of pSS is favorable, quality of life is typically reduced due to the diverse manifestations of the disease. The aim of this study is to compare the salivary metabolomes of pSS with healthy controls (HCs). Seven cases were selected from a cohort of pSS patients, and six age- and sex-matched HCs were recruited from a cohort of volunteers. Whole unstimulated saliva was collected for NMR analysis. Our metabolomic analysis focused on 360 ms total echo 1D 1H NMR CPMG spectra. Metabolites detected with CPMG NMR spectra were assigned through 2D NMR spectra (COSY, TOCSY, and HSQC). About 50 metabolites were detected and assigned. Unsupervised exploratory PCA returned partial clustering, and PLS-DA improved the separation between pSS and HCs, highlighting a pool of metabolites distinctly describing each group. Despite the limited number of samples, the presented preliminary data are promising. PLS-DA indicated well-defined group separation, suggesting that the application of 1H-NMR metabolomics is suitable for the study of pSS. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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Review

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25 pages, 2122 KiB  
Review
Saliva as Biomarker for Oral and Chronic Degenerative Non-Communicable Diseases
by Michele Basilicata, Massimo Pieri, Giulia Marrone, Eleonora Nicolai, Manuela Di Lauro, Vincenza Paolino, Flaminia Tomassetti, Ilaria Vivarini, Patrizio Bollero, Sergio Bernardini and Annalisa Noce
Metabolites 2023, 13(8), 889; https://doi.org/10.3390/metabo13080889 - 27 Jul 2023
Cited by 6 | Viewed by 2420
Abstract
Saliva is a very complex fluid and it is essential to maintain several physiological processes and functions, including oral health, taste, digestion and immunological defenses. Saliva composition and the oral microbiome can be influenced by several factors, like diet and smoking habits, and [...] Read more.
Saliva is a very complex fluid and it is essential to maintain several physiological processes and functions, including oral health, taste, digestion and immunological defenses. Saliva composition and the oral microbiome can be influenced by several factors, like diet and smoking habits, and their alteration can represent an important access point for pathogens and, thus, for systemic illness onset. In this review, we explore the potentiality of saliva as a new tool for the early detection of some pathological conditions, such as oral diseases, chronic degenerative non-communicable diseases, among these chronic kidney disease (CKD). We also examined the possible correlation between oral and systemic diseases and oral and gut microbiota dysbiosis. In particular, we deeply analyzed the relationship between oral diseases and CKD. In this context, some salivary parameters can represent a new device to detect either oral or systemic pathologies. Moreover, the positive modulation of oral and gut microbiota induced by prebiotics, postbiotics, or symbiotics could represent a new possible adjuvant therapy in the clinical management of oral diseases and CKD. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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14 pages, 871 KiB  
Review
Oral Sources of Salivary Metabolites
by Eelis Hyvärinen, Bina Kashyap and Arja M. Kullaa
Metabolites 2023, 13(4), 498; https://doi.org/10.3390/metabo13040498 - 29 Mar 2023
Cited by 13 | Viewed by 2398
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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15 pages, 1487 KiB  
Review
Saliva Metabolomic Profile in Dental Medicine Research: A Narrative Review
by Konstantinos Tzimas and Eftychia Pappa
Metabolites 2023, 13(3), 379; https://doi.org/10.3390/metabo13030379 - 3 Mar 2023
Cited by 10 | Viewed by 2799
Abstract
Metabolomic research tends to increase in popularity over the years, leading to the identification of new biomarkers related to specific health disorders. Saliva is one of the most newly introduced and systematically developed biofluids in the human body that can serve as an [...] Read more.
Metabolomic research tends to increase in popularity over the years, leading to the identification of new biomarkers related to specific health disorders. Saliva is one of the most newly introduced and systematically developed biofluids in the human body that can serve as an informative substance in the metabolomic profiling armamentarium. This review aims to analyze the current knowledge regarding the human salivary metabolome, its alterations due to physiological, environmental and external factors, as well as the limitations and drawbacks presented in the most recent research conducted, focusing on pre—analytical and analytical workflows. Furthermore, the use of the saliva metabolomic profile as a promising biomarker for several oral pathologies, such as oral cancer and periodontitis will be investigated. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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10 pages, 751 KiB  
Review
Salivary Metabolomics in the Diagnosis and Monitoring of Neurodegenerative Dementia
by Eelis Hyvärinen, Eino Solje, Jouko Vepsäläinen, Arja Kullaa and Tuulia Tynkkynen
Metabolites 2023, 13(2), 233; https://doi.org/10.3390/metabo13020233 - 4 Feb 2023
Cited by 7 | Viewed by 2866
Abstract
Millions of people suffer with dementia worldwide. However, early diagnosis of neurodegenerative diseases/dementia (NDD) is difficult, and no specific biomarkers have been found. This study aims to review the applications of salivary metabolomics in diagnostics and the treatment monitoring of NDD A literature [...] Read more.
Millions of people suffer with dementia worldwide. However, early diagnosis of neurodegenerative diseases/dementia (NDD) is difficult, and no specific biomarkers have been found. This study aims to review the applications of salivary metabolomics in diagnostics and the treatment monitoring of NDD A literature search of suitable studies was executed so that a total of 29 original research articles were included in the present review. Spectroscopic methods, mainly nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, give us a broad view of changes in salivary metabolites in neurodegenerative diseases. The role of different salivary metabolites in brain function is discussed. Further studies with larger patient cohorts should be carried out to investigate the association between salivary metabolites and brain function and thus learn more about the complicated pathways in the human body. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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Other

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59 pages, 7400 KiB  
Commentary
Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part III: Implementations for the Diagnosis of Non-Cancerous Disorders, Both Oral and Systemic
by Martin Grootveld, Georgina Page, Mohammed Bhogadia, Kayleigh Hunwin and Mark Edgar
Metabolites 2023, 13(1), 66; https://doi.org/10.3390/metabo13010066 - 1 Jan 2023
Cited by 4 | Viewed by 3178
Abstract
This communication represents Part III of our series of reports based on the applications of human saliva as a useful and conveniently collectable medium for the discovery, identification and monitoring of biomarkers, which are of some merit for the diagnosis of human diseases. [...] Read more.
This communication represents Part III of our series of reports based on the applications of human saliva as a useful and conveniently collectable medium for the discovery, identification and monitoring of biomarkers, which are of some merit for the diagnosis of human diseases. Such biomarkers, or others reflecting the dysfunction of specific disease-associated metabolic pathways, may also be employed for the prognostic pathological tracking of these diseases. Part I of this series set the experimental and logistical groundwork for this report, and the preceding paper, Part II, featured the applications of newly developed metabolomics technologies to the diagnosis and severity grading of human cancer conditions, both oral and systemic. Clearly, there are many benefits, both scientific and economic, associated with the donation of human saliva samples (usually as whole mouth saliva) from humans consenting to and participating in investigations focused on the discovery of biomolecular markers of diseases. These include usually non-invasive collection protocols, relatively low cost when compared against blood sample collection, and no requirement for clinical supervision during collection episodes. This paper is centred on the employment and value of ‘state-of-the-art’ metabolomics technologies to the diagnosis and prognosis of a wide range of non-cancerous human diseases. Firstly, these include common oral diseases such as periodontal diseases (from type 1 (gingivitis) to type 4 (advanced periodontitis)), and dental caries. Secondly, a wide range of extra-oral (systemic) conditions are covered, most notably diabetes types 1 and 2, cardiovascular and neurological diseases, and Sjögren’s syndrome, along with a series of viral infections, e.g., pharyngitis, influenza, HIV and COVID-19. Since the authors’ major research interests lie in the area of the principles and applications of NMR-linked metabolomics techniques, many, but not all, of the studies reviewed were conducted using these technologies, with special attention being given to recommended protocols for their operation and management, for example, satisfactory experimental model designs; sample collection and laboratory processing techniques; the selection of sample-specific NMR pulse sequences for saliva analysis; and strategies available for the confirmation of resonance assignments for both endogenous and exogenous molecules in this biofluid. This article also features an original case study, which is focussed on the use of NMR-based salivary metabolomics techniques to provide some key biomarkers for the diagnosis of pharyngitis, and an example of how to ‘police’ such studies and to recognise participants who perceive that they actually have this disorder but do not from their metabolic profiles and multivariate analysis pattern-based clusterings. The biochemical and clinical significance of these multidimensional metabolomics investigations are discussed in detail. Full article
(This article belongs to the Special Issue Salivary Metabolomics for Oral and Systemic Diseases Volume 2)
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