Salivary Biomarkers and Their Application to Diagnosis and Monitoring Human Diseases

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 26544

Special Issue Editor

Department of Nursing, University of Valencia, 46010 Valencia, Spain
Interests: cognitive impairment; frailty syndrome; neurodevelopemntal disorders; depression; neuropathy; sleep; envirnomental factors; comorbidty; immune alterations; metabolic alterations; biomarkers
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Special Issue Information

Dear Colleagues,

Among biological fluids, saliva is achieving great improtance in diagnostic not only for oral diseases but also for systemic diseases. Its collection is fast, easy, inexpensive, and non-invasive. In addition, saliva, as a "mirror of the body," can reflect the physiological and pathological state of the body. Therefore, its use as a diagnostic and monitoring tool in many fields of science such as medicine, dentistry, and pharmacotherapy is growing up. Published data on "Salivaomics" including various "omics" constituents of saliva such as the proteome, transcriptome, micro-RNA, metabolome, and microbiome has grown up during the lasta decade leading to the development of new technologies and the validation a wide range of salivary biomarkers that will soon make the use of saliva as a useful tool in clinical practice.

You may choose our Joint Special Issue in International Journal of Molecular Sciences.

Prof. Dr. Omar Cauli
Guest Editor

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Keywords

  • cytokines
  • energetic metabolism
  • enzymes
  • neurotrophins
  • hormones
  • proteomic
  • electrophoresis
  • biomarkers
  • pollutants

Published Papers (7 papers)

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Research

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14 pages, 1287 KiB  
Article
Comparison of Periodontopathic Bacterial Profiles of Different Periodontal Disease Severity Using Multiplex Real-Time Polymerase Chain Reaction
by Jin Uk Choi, Jun-Beom Lee, Kyoung-Hwa Kim, Sungtae Kim, Yang-Jo Seol, Yong-Moo Lee and In-Chul Rhyu
Diagnostics 2020, 10(11), 965; https://doi.org/10.3390/diagnostics10110965 - 17 Nov 2020
Cited by 7 | Viewed by 2348
Abstract
Periodontopathic bacteria are known to have a pivotal role in the pathogenesis of periodontitis. The aim of the study was to quantitatively compare bacterial profile of patients with different severity of periodontal disease using samples from mouthwash and the subgingival area. Further analysis [...] Read more.
Periodontopathic bacteria are known to have a pivotal role in the pathogenesis of periodontitis. The aim of the study was to quantitatively compare bacterial profile of patients with different severity of periodontal disease using samples from mouthwash and the subgingival area. Further analysis was performed to evaluate the correlation between mouthwash and two subgingival sampling methods: paperpoint and gingival retraction cord; 114 subjects enrolled in the study, and were divided equally into three groups according to disease severity. Mouthwash and subgingival sampling were conducted, and the samples were quantitatively analyzed for 11 target periodontopathic bacteria using multiplex real-time PCR. There were statistically significant differences in bacterial counts and prevalence of several species between the study groups. Mouthwash sampling showed significant correlations with two different subgingival sampling methods in regard to the detection of several bacteria (e.g., ρ = 0.793 for Porphyromonas gingivalis in severe periodontitis), implying that mouthwash sampling can reflect subgingival microbiota. However, the correlation was more prominent as disease severity increased. Although bacteria in mouthwash have potential to become a biomarker, it may be more suitable for the diagnosis of severe periodontitis, rather than early diagnosis. Further research is required for the discovery of biomarkers for early diagnosis of periodontitis. Full article
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11 pages, 955 KiB  
Article
Salivary Alpha-Amylase in Experimentally-Induced Muscle Pain
by Nikolaos Christidis, Pegah Baghernejad, Aylin Deyhim and Hajer Jasim
Diagnostics 2020, 10(9), 722; https://doi.org/10.3390/diagnostics10090722 - 20 Sep 2020
Cited by 6 | Viewed by 2714
Abstract
Salivary alpha-amylase (sAA) is a marker of psychological stress and might also be a potential marker for pain-associated stress due its non-invasive, cost-effective, and stress-free collection. The current study aimed to investigate whether the levels of sAA are influenced by experimentally induced muscle [...] Read more.
Salivary alpha-amylase (sAA) is a marker of psychological stress and might also be a potential marker for pain-associated stress due its non-invasive, cost-effective, and stress-free collection. The current study aimed to investigate whether the levels of sAA are influenced by experimentally induced muscle pain. In this study, 26 healthy, pain-free and age-matched participants (23.8 ± 2.6 years) were included, 13 women and 13 men. Prior to the experiment, questionnaires assessing health and anxiety were completed. Muscle pain was then induced through intramuscular injection of 0.4 mL hypertonic saline (56.5 mg/mL) into the masseter muscle and unstimulated whole saliva samples were collected at baseline before injection, 2 min, and 15 min after injection. A commercially available colorimetric assay was used to analyze the sAA. Perceived pain and stress were assessed using a 0–100 Numeric Rating Scale for each sample. There were no significant differences in sAA levels prior and after injection of hypertonic saline (p > 0.05) although sAA levels showed a slight decrease during experimentally-induced muscle pain. However, a strong correlation was observed between self-reported pain and perceived level of stress during experimentally-induced muscle pain (r2 = 0.744; p < 0.0001). Furthermore, there was a moderate correlation between the levels of sAA at baseline and during experimental pain (r2 = 0.687; p < 0.0001). In conclusion, this study could not show any association between the levels of sAA and perceived pain and or/stress. However, since a significant strong correlation could be observed between perceived stress and pain intensity, this study indicates that experimentally-induced muscle pain could be used as a stress model. Full article
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9 pages, 686 KiB  
Article
Unstimulated Parotid Saliva Sampling in Juvenile Idiopathic Arthritis and Healthy Controls: A Proof-of-Concept Study on Biomarkers
by Alexandra Dimitrijevic Carlsson, Bijar Ghafouri, Carin Starkhammar Johansson and Per Alstergren
Diagnostics 2020, 10(4), 251; https://doi.org/10.3390/diagnostics10040251 - 24 Apr 2020
Cited by 2 | Viewed by 3611
Abstract
The aims of this proof-of-concept study were to develop a collecting method for unstimulated parotid saliva in juvenile idiopathic arthritis (JIA) patients and healthy children and to investigate if inflammatory biomarkers could be detected in these samples. Forty-five children with JIA (median age [...] Read more.
The aims of this proof-of-concept study were to develop a collecting method for unstimulated parotid saliva in juvenile idiopathic arthritis (JIA) patients and healthy children and to investigate if inflammatory biomarkers could be detected in these samples. Forty-five children with JIA (median age of 12 years and 25th–75th percentile of 10–15 years; 33 girls and 12 boys) and 16 healthy children as controls (median age of 13 years and 25–75th percentile of 10–13 years; 11 girls and 5 boys) were enrolled in this study. Unstimulated parotid saliva was collected with a modified Carlson–Crittenden collector. The salivary flow rate and salivary concentrations of total protein and inflammatory mediators were assessed. The Meso Scale Discovery electrochemiluminescence immunoassay was used for analyzing protein concentrations and the inflammatory biomarkers. Sufficient parotid saliva volumes to be analyzed could be collected with the collection device. JIA patients had a lower sampling saliva volume (p = 0.008) and saliva flow rate (p = 0.039) than controls. The total protein concentrations and inflammatory biomarkers were measured in the last six healthy subjects. The median protein concentration was 1312 µg/mL (25th percentile: 844 µg/mL and 75th percentile: 2062 µg/mL; n = 6) and quantifiable concentrations of 39 inflammatory proteins could be assessed in these samples. In conclusion, this study indicates that the saliva sampling method, as used in the present study, is able to collect sufficient sample volumes in children, and that it is possible to analyze various inflammatory biomarkers in the collected saliva. Full article
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Review

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20 pages, 635 KiB  
Review
Changes in Salivary Amylase and Glucose in Diabetes: A Scoping Review
by Pilar Pérez-Ros, Emmanuel Navarro-Flores, Ivan Julián-Rochina, Francisco Miguel Martínez-Arnau and Omar Cauli
Diagnostics 2021, 11(3), 453; https://doi.org/10.3390/diagnostics11030453 - 06 Mar 2021
Cited by 24 | Viewed by 5062
Abstract
Background and Objective: Diabetes mellitus (DM) is a common long-term disease which can be related with salivary amylase levels. DM has recently been associated with salivary amylase diagnostics that could further impair diagnoses in the diabetic population, as well as being an interesting [...] Read more.
Background and Objective: Diabetes mellitus (DM) is a common long-term disease which can be related with salivary amylase levels. DM has recently been associated with salivary amylase diagnostics that could further impair diagnoses in the diabetic population, as well as being an interesting alternative to traditional methods of determine glucose levels. The main advantage of this method is related to the fact that it is a fast diagnostic method. The DM population experiences changes to their metabolism which affects their salivary parameters, making this an alternative procedure for diagnosis and follow-up of the illness due to the non-invasive nature of salivary analyzes. The objective of this review is to summarize the evidence regarding the changes in salivary amylase and glucose levels, and their relationship with blood markers of glycemic control used in clinical settings such as blood glucose and glycated hemoglobin. The differences in salivary amylase levels depending on the method of saliva collection under fasting or non-fasting conditions. The changes in salivary amylase depends on the type of diabetes, the type of insulin treatment or the quality of glycemic control. Conclusions: Salivary amylase concentration is increased in diabetic patients in most of the studies and salivary glucose concentration in all studies in both fasting and non-fasting (post-prandial) conditions. Salivary amylase and glucose concentration represent potential non-invasive biomarkers to evaluate glycemic control and clinical management of diabetic patients, although it is necessary to evaluate the influence of potential modulating factors such as age, duration diseases, sex and the effects of pharmacological treatments in these outcomes which remained to be elucidated. Full article
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22 pages, 356 KiB  
Review
The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease
by Patrycja Pawlik and Katarzyna Błochowiak
Diagnostics 2021, 11(2), 371; https://doi.org/10.3390/diagnostics11020371 - 22 Feb 2021
Cited by 22 | Viewed by 4007
Abstract
Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms [...] Read more.
Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms. Full article
19 pages, 753 KiB  
Review
Salivary Inflammatory Molecules as Biomarkers of Sleep Alterations: A Scoping Review
by Vanessa Ibáñez-del Valle, Rut Navarro-Martínez, Maria Luisa Ballestar-Tarín and Omar Cauli
Diagnostics 2021, 11(2), 278; https://doi.org/10.3390/diagnostics11020278 - 10 Feb 2021
Cited by 7 | Viewed by 3534
Abstract
Poor sleep quality and sleep disorders are the most common problems in people, affecting health-related quality of life. Various studies show an association between sleep disorders and altered levels of stress hormones and inflammatory cytokines measured in saliva. The main objective of this [...] Read more.
Poor sleep quality and sleep disorders are the most common problems in people, affecting health-related quality of life. Various studies show an association between sleep disorders and altered levels of stress hormones and inflammatory cytokines measured in saliva. The main objective of this article is to provide an analysis of the current evidence related to changes in inflammatory markers in the saliva and their associations with sleep quality measurement (both objective and subjective methods) in healthy subjects and in sleep-related disorders. To that end, a scoping review was carried out, following the PRISMA criteria in the bibliographic search in several databases: PubMed, EBSCO, and SCOPUS. Eleven of the articles are from the adult population and two from the child-youth population. They mainly measure the relationship between sleep and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) alpha, as well as other inflammatory markers such as myeloperoxidase (MPO) and prostaglandin-endoperoxide synthase 2. An analysis shows the relationship between these salivary biomarkers and sleep quality, especially in the case of IL-6 in both healthy subjects and several pathologies associated with sleep-disorders. The results for TNFα and IL-1β measurements are still inconclusive and the difference with IL-6 was assessed. Two studies reported interventions that result in sleep improvement and are accompanied by the normalization of inflammatory changes detected in the saliva. As it is an easy-to-apply and non-invasive method, the measurement of salivary cytokines can be very useful in chronobiology studies. Further studies are required to determine the sensitivity of salivary inflammatory markers in monitoring biological rhythms and acting as biomarkers in the detection of sleep disorders and sleep interventions. Full article
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14 pages, 300 KiB  
Review
Application of Salivary Biomarkers in the Diagnosis of Fibromyalgia
by Rebeca Illescas-Montes, Víctor J. Costela-Ruiz, Lucía Melguizo-Rodríguez, Elvira De Luna-Bertos, Concepción Ruiz and Javier Ramos-Torrecillas
Diagnostics 2021, 11(1), 63; https://doi.org/10.3390/diagnostics11010063 - 03 Jan 2021
Cited by 7 | Viewed by 4182
Abstract
Fibromyalgia (FM) is a highly prevalent syndrome that impairs the quality of life of the patients; however, its diagnosis is complex and mainly centered on pain symptoms. The study of salivary biomarkers has proven highly useful for the diagnosis and prognosis of numerous [...] Read more.
Fibromyalgia (FM) is a highly prevalent syndrome that impairs the quality of life of the patients; however, its diagnosis is complex and mainly centered on pain symptoms. The study of salivary biomarkers has proven highly useful for the diagnosis and prognosis of numerous diseases. The objective of this review was to gather published data on the utilization of salivary biomarkers to facilitate and complement the diagnosis of FM. Salivary biomarkers used in FM diagnosis include cortisol; calgranulin; and the enzymes α-amylase, transaldolase, and phosphoglycerate mutase. Increased serum levels of C-reactive protein, cytokines interleukin 1-β, interleukin 6, interleukin 8, interleukin 10, interleukin 17, tumor necrosis factor α, and various chemokines may serve as salivary biomarkers, given observations of their increased serum levels in patients with FM. Further research is warranted to study in depth the role and performance of biomarkers currently used in FM diagnosis/prognosis and to identify novel salivary biomarkers for this disease. Full article
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