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

Maria Herrala,Jopi J W Mikkonen,Sami Myllymaa,Tuula Salo,Hubertus Seitsalo,Kati Hanhineva,Raija K Niemelä,Leo Tjäderhane,Reijo Lappalainen,Marko Lehtonen,Soile Turunen,Arja M Kullaa,Olli Kärkkäinen

doi:10.3390/metabo11090595

Abstract

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.

Highlights

Saliva is an essential biofluid in the oral cavity, and its composition and volume are important factors in oral health
Metabolites 2021, 11, 595 the saliva metabolite profile of the healthy control (HC). Primary Sjögren’s syndrome (pSS) patients with low-dose doxycycline (LDD) treatment were mixed with the first two groups in the principal component analysis (PCA), indicating that the doxycycline treatment shifted the saliva metabolite profile closer to that seen in the HC compared to the untreated pSS patients
Good predictability is seen in the partial least sum of squares discriminant analysis (PLS-DA) model between the saliva metabolite profiles of the HC and the untreated pSS patients (PLS-DA model with three components, Q2 = 0.77), indicating a clear separation of the saliva metabolite profiles, in line with the PCA results

Summary

Introduction

Saliva is an essential biofluid in the oral cavity, and its composition and volume are important factors in oral health. Many factors, including systemic diseases, can affect salivary production. Sjögren’s syndrome (SS) is a disease that affects salivary glands, manifesting as hyposalivation and abnormal levels of salivary components [2]. Sjögren’s syndrome can be classified as primary (pSS) or secondary (sSS) forms. 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. There is an urgent need to study and develop new tools for the diagnosis and monitoring of pSS

Methods

Results

Conclusion