University of Oulu

Herrala, M.; Turunen, S.; Hanhineva, K.; Lehtonen, M.; Mikkonen, J.J.W.; Seitsalo, H.; Lappalainen, R.; Tjäderhane, L.; Niemelä, R.K.; Salo, T.; Myllymaa, S.; Kullaa, A.M.; Kärkkäinen, O. Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren’s Syndrome. Metabolites 2021, 11, 595.

Low-dose doxycycline treatment normalizes levels of some salivary metabolites associated with oral microbiota in patients with primary Sjögren’s syndrome

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Author: Herrala, Maria1,2,3; Turunen, Soile4; Hanhineva, Kati5,6;
Organizations: 1Research Group of Oral Health Sciences, Faculty of Medicine, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
2Institute of Dentistry, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland
3Medical Research Center Oulu, Oulu University Hospital, University of Oulu, 90014 Oulu, Finland
4School of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland
5Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland
6Department of Life Technologies, Food Chemistry and Food Development Unit, University of Turku, 20014 Turku, Finland
7Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland
8Private Dental Clinic Hammas&Hammas, 00130 Helsinki, Finland
9Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
10Department of Rheumatology, Oulu University Hospital, 90220 Oulu, Finland
11Translational Immunology Research Program (TRIMM), University of Helsinki, 00014 Helsinki, Finland
12Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki University Hospital, 00014 Helsinki, Finland
13Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
14Diagnostic Imaging Center, Kuopio University Hospital, 70029 Kuopio, Finland
15Educational Dental Clinic, Kuopio University Hospital, 90220 Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-11-19


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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Series: Metabolites
ISSN: 2218-1989
ISSN-E: 2218-1989
ISSN-L: 2218-1989
Volume: 11
Issue: 9
Article number: 595
DOI: 10.3390/metabo11090595
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
313 Dentistry
Funding: The Finnish Funding Agency for Technology and Innovation (Tekes), a project called Oraldent (2186/31/2010), and Oral Cancer (52/31/2014) funded part of this study. M.H. received a personal grant from the Finnish Dental Society, Apollonia.
Copyright information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (