Variability of salivary metabolite levels in patients with Sjögren’s syndrome

Abstract

Purpose: To investigate inter-and intra-individual variation in the levels and outputs (concentration multiplied by salivary flow rate) of salivary metabolites in patients with primary Sjögren's syndrome (pSS). Methods: A total of 56 samples of stimulated saliva were collected from 14 female pSS patients during four laboratory visits within 20 weeks and analyzed using proton nuclear magnetic resonance spectroscopy. Single saliva samples from each of 15 controls were also analyzed. Results: Among 21 quantified metabolites, choline was significantly elevated in the pSS patients at each time point (P ≤ 0.015), taurine at the last three time points (P ≤ 0.013), alanine at the last two time points (P ≤ 0.007) and glycine at the last time point (P = 0.005). Inter-individual variation in metabolite concentrations was generally larger among the patients than among the controls, and significantly large variations were observed for glycine (P ≤ 0.007, all time points), choline (P ≤ 0.033, three last time points) and alanine (P = 0.028, baseline). Metabolite output analysis showed that choline had the lowest intra-patient variation. Conclusion: In spite of considerable intra-and inter-individual variation, levels and outputs of specific metabolites in patients with pSS differ from those in controls, and may be potentially applicable as new biological markers for monitoring of the response to treatment.

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

“…Eating and drinking were not allowed a minimum of one hour before the saliva sample collection. After collection, the saliva samples were immediately centrifuged and the supernatants were stored and transported as described in [ 6 , 9 ]. We demonstrate this study design in Figure 3 .…”

“…Because patients typically suffer from hyposalivation, some samples were not sufficient for analysis with LC-MS or were poor quality. Saliva flow rates (mL/min) were calculated immediately after collection, as described previously (Herrala et al, (2021)). The Wilcoxon signed ranks test was used to analyze the salivary flow rate between the pre-medication and one week medication samples.…”

“…The metabolic profile of saliva can provide an early diagnosis of pSS and monitoring of its progress [ 6 ]. SS is associated with alterations in the metabolite profile of saliva; for example, elevated levels of choline, taurine, and alanine have been reported [ 6 , 7 ].…”

“…The metabolic profile of saliva can provide an early diagnosis of pSS and monitoring of its progress [ 6 ]. SS is associated with alterations in the metabolite profile of saliva; for example, elevated levels of choline, taurine, and alanine have been reported [ 6 , 7 ]. Recent developments in instrumentation have led to new spectrometric platforms for metabolomics, which employ state-of-the-art analytical techniques, such as different mass spectrometry methods in conjunction with either high-performance liquid chromatography (HPLC-MS) or two-dimensional gas chromatography (2DGC-MS) and nuclear magnetic resonance (NMR) spectroscopy [ 8 ].…”

Aging-Related Metabolic Dysfunction in the Salivary Gland: A Review of the Literature

“…Because aging is a complex process that is influenced by a combination of genetics, the environment, diet, and lifestyles, metabolomics are becoming powerful tools to analyze the myriad of interactions and generate profiles of aging-related alterations in the body, thus providing better information about novel pathways and biomarkers and improving clinical approaches [ 22 ]. In the narrow field of salivary gland-related metabolomics studies, the majority of these studies focused on the discovery of disease biomarkers, from salivary gland-related diseases such as Sjögren’s syndrome to oral and periodontal diseases and to neurodegenerative diseases such as dementia, Alzheimer’s disease, and even cancers [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. In Sjögren’s syndrome, metabolomics research using nuclear magnetic resonance (NMR) revealed that the concentrations of choline, taurine, alanine, glycine, butyrate, phenylalanine, and proline increased significantly in the saliva samples of Sjögren’s syndrome patients compared with healthy candidates.…”