Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren’s Syndrome
Maria Herrala,
Soile Turunen,
Kati Hanhineva,
Marko Lehtonen,
Jopi J. W. Mikkonen,
Hubertus Seitsalo,
Reijo Lappalainen,
Leo Tjäderhane,
Raija K. Niemelä,
Tuula Salo,
Sami Myllymaa,
Arja M. Kullaa,
Olli Kärkkäinen
Affiliations
Maria Herrala
Research Group of Oral Health Sciences, Faculty of Medicine, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
Soile Turunen
School of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland
Kati Hanhineva
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland
Marko Lehtonen
School of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland
Jopi J. W. Mikkonen
Institute of Dentistry, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland
Hubertus Seitsalo
Private Dental Clinic Hammas&Hammas, 00130 Helsinki, Finland
Reijo Lappalainen
Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland
Leo Tjäderhane
Medical Research Center Oulu, Oulu University Hospital, University of Oulu, 90014 Oulu, Finland
Raija K. Niemelä
Department of Rheumatology, Oulu University Hospital, 90220 Oulu, Finland
Tuula Salo
Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
Sami Myllymaa
Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland
Arja M. Kullaa
Research Group of Oral Health Sciences, Faculty of Medicine, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
Olli Kärkkäinen
School of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland
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.