Discovery of putative salivary biomarkers for Sjögren’s syndrome using high resolution mass spectrometry and bioinformatics

Zoukhri, Driss; Rawe, Ian; Singh, Mabi; Brown, Ashley; Kublin, Claire L.; Dawson, Kevin J.; Haddon, William; White, Earl L.; Hanley, Kathleen M.; Tusé, Daniel; Malyj, Wasyl; Papas, Athena

doi:10.2334/josnusd.54.61

Cited by 6 publications

(8 citation statements)

References 41 publications

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“…In addition, food debris is retained longer, prolonging the pH drop. We have found increased levels of proline-rich phosphoproteins in the saliva of Sjögren’s subjects (Zoukhri et al 2012). Saliva delivers statherin, proline-rich proteins, and other mucinous proteins that bind to negatively charged hydroxyapatite to immediately form an acquired enamel pellicle.…”

Section: Discussionmentioning

confidence: 93%

Characterizing Microbiota from Sjögren’s Syndrome Patients

Singh

Teles

Uzel

et al. 2020

JDR Clinical & Translational Research

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Objective: To compare the oral microbiota of Sjögren’s syndrome (SS) with that of healthy subjects (HS). Methods: Supragingival and subgingival biofilm samples were collected from the mesial-buccal tooth surfaces of SS patients (n = 57) and age- and sex-matched HS (n = 53). Unstimulated saliva and 8 oral tissue samples were taken using a buccal brush. Caries and periodontal measures were recorded. All supragingival samples and a subgroup of 24 SS and 28 HS subgingival samples, as well as 32 SS and 11 HS saliva and oral tissue samples, were analyzed for their content of 41 bacterial species using checkerboard DNA-DNA hybridization. Mean levels (×105 ± SEM) and percentage of DNA probe counts of each species were determined for each sample site and averaged within subjects in the 2 clinical groups. Kruskal-Wallis tests, adjusting for multiple comparisons and cluster analysis, were used for soft tissue and microbial analysis, and the Mann-Whitney test was used to compare caries and periodontal measures. Results: Mean (×105 ± SEM) total DNA probe counts in supragingival samples were significantly lower (P < 0.001) in the SS (13.3 ± .7) compared to the HS (44.1 ± 6.8) group. In supragingival samples, Veillonella parvula, Fusobacterium nucleatum ss vincenti, and Propionibacterium acnes were markedly elevated in the SS compared to the HS group in both mean (×105 ± SEM) and mean (± SEM) percentage DNA probe counts (P < 0.001). In subgingival samples of SS, V. parvula was significantly different compared to HS (P < 0.05). SS was characterized by high levels of purple and low levels of orange and red complexes. Cluster analysis of oral tissues and saliva demonstrated that the mean microbial profiles for SS patients and the HS group clustered separately. Active root caries (P < 0.003) and attachment loss were significantly higher (P < 0.029) in the SS group compared to the HS group. Conclusion: These findings indicate that saliva is a major controlling factor of intraoral biofilm. V. parvula may be a unique microbial biomarker for Sjögren’s syndrome. Knowledge Transfer Statement The microbiome characterized for Sjögren’s syndrome in salivary hypofunction is shown to be under stress and reduced. Veillonella parvula can be a possible identification of a biomarker for Sjögren’s syndrome.

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Section: Discussionmentioning

confidence: 93%

Characterizing Microbiota from Sjögren’s Syndrome Patients

Singh

Teles

Uzel

et al. 2020

JDR Clinical & Translational Research

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“…The focus of this article is pSS. SS has a wide range of clinical manifestations and symptoms, from affecting salivary or lacrimal glands to multi-organ symptoms and, potentially, a high risk of malignant lymphomas [ 3 , 4 ]. Patients with pSS usually have to wait a long time for a diagnosis, during which the disease progresses.…”

Section: Introductionmentioning

confidence: 99%

Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren’s Syndrome

et al. 2021

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Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjögren’s syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples (n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples (n = 10) of non-treated female patients with pSS, and saliva samples (n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS.

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“…Our lab has performed extensive research on the mechanisms involved in dry eye and dry mouth in human and animal models of Sjögren's syndrome [14–19]. We reported that stem/progenitor cells were present in the murine lacrimal gland and the number of these cells increased during the repair phase after experimentally induced inflammation [16].…”

Section: Introductionmentioning

confidence: 99%

Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren’s Syndrome

Aluri

Samizadeh

Edman

et al. 2017

Stem Cells International

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The purpose of the present study was to test the potential of mouse bone marrow-derived mesenchymal stem cells (BD-MSCs) in improving tear production in a mouse model of Sjögren's syndrome dry eye and to investigate the underlying mechanisms involved. NOD mice (n = 20) were randomized to receive i.p. injection of sterile phosphate buffered saline (PBS, control) or murine BD-MSCs (1 × 106 cells). Tears production was measured at baseline and once a week after treatment using phenol red impregnated threads. Cathepsin S activity in the tears was measured at the end of treatment. After 4 weeks, animals were sacrificed and the lacrimal glands were excised and processed for histopathology, immunohistochemistry, and RNA analysis. Following BD-MSC injection, tears production increased over time when compared to both baseline and PBS injected mice. Although the number of lymphocytic foci in the lacrimal glands of treated animals did not change, the size of the foci decreased by 40.5% when compared to control animals. The mRNA level of the water channel aquaporin 5 was significantly increased following delivery of BD-MSCs. We conclude that treatment with BD-MSCs increases tear production in the NOD mouse model of Sjögren's syndrome. This is likely due to decreased inflammation and increased expression of aquaporin 5.

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Discovery of putative salivary biomarkers for Sjögren’s syndrome using high resolution mass spectrometry and bioinformatics

Cited by 6 publications

References 41 publications

Characterizing Microbiota from Sjögren’s Syndrome Patients

Characterizing Microbiota from Sjögren’s Syndrome Patients

Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren’s Syndrome

Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren’s Syndrome

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