Sjögren’s syndrome (SS) is a systemic chronic autoimmune disease, which touches connective tissues (André and Böckle, 2022). It has been established that 1-3% of the general population may suffer from this disease (Bayetto and Logan, 2010). Often, it is diagnosed between the 5th and the 7th decade of life and occurs eight times more frequently (about eight times more often) in women than in men (Bayetto and Logan, 2010; André and Böckle, 2022). The etiology of this disease is unknown, but environmental factors are suspected to play a key role (André and Böckle, 2022). Risk factors include viral diseases (Epstein-Barr virus, HCV, human lymphocyte leukemia virus), genetic predisposition and sex hormones (Bayetto and Logan, 2010). However, the greatest impact appears to be exerted by the Epstein-Barr virus, which is found in biopsy materials taken from the lacrimal glands, as well as in salivary gland and saliva specimens (Negrini et al., 2022).Viral infection most likely promote the production of auto-antibodies, ultimately leading to cross-reactivity of immune elements with host antigens (Bayetto and Logan, 2010). It is assumed that the genetic predisposition to Sjögren’s syndrome can be diagnosed if this disease occurs in at least two family members (Bayetto and Logan, 2010). The relationships between polymorphic major histocompatibility complex (MHC) genes are expected to play an important role here (Bayetto and Logan, 2010).The disproportion in the incidence of SS allows us to put forward the theory that sex hormones play an important role in etiology. Research show that estrogens influence the immune response by increasing the production of antibodies by B cells. The menopause period in women is the most common age range in which SS occurs, which may indicate an indirect effect of estrogens on the development of this disease (Bayetto and Logan, 2010).

Sjögren’s syndrome could be primary (pSS) or secondary (sSS) but both is likely similar (Bayetto and Logan, 2010). Their difference resides in that sSS is an element of other autoimmune diseases, most often systemic lupus erythematosus (15-36%), rheumatoid arthritis (20-32%) or progressive and limited systemic sclerosis (11-24%) (Stefanski et al., 2017). pSS is not correlated with any autoimmune diseases (Bayetto and Logan, 2010). There are general symptoms of dryness, known as dryness syndrome (xerostomia, xerophthalmia) (Bayetto and Logan, 2010; Zeron et al., 2013). The pathogenesis is still unknown (Negrini et al., 2022). However, the main role in the development might be played by elements of the immune system (T and B cells) (Bayetto and Logan, 2010; Tian et al., 2021). Excessive activation of B cells located in the exocrine glands causes the production of anti-SSA and anti-SSB autoantibodies (0–70% patients with pSS) (Bayetto and Logan, 2010; Tian et al., 2021). T cells, on the other hand, infiltrate the exocrine glands and increase the extremity of cytokines, thus leading to damage to the lobular cells and ultimately to xerostomia (Tian et al., 2021).

The concerns of Sjögren’s syndrome center on disorders of the exocrine glands (Tian et al., 2021). Most commonly, patients report symptoms such as dry eyes and dry mouth (89% of them experience both) (Negrini et al., 2022). In the aspect of the oral cavity, dysphagia, pain and burning are frequently noticeable, which is related to reduced saliva production (Negrini et al., 2022). Often, a physical examination also reveals dental caries and periodontal disease, as well as frequently recurrent Candida albicans infections (occurring 10 times more often than in the normal population) (Stefanski et al., 2017; Negrini et al., 2022). In sSS, symptoms of fatigue and joint pain may also manifest (6). Usually treating Sjögren’s syndrome is symptomatic (Baer and Walitt, 2018). It is crucial to stay hydrated, quit smoking, apply fluoride to prevent dental caries and avoid fatigue (among others, good sleep hygiene) (Baer and Walitt, 2018). Pharmacological treatment typically relies on muscarinic agonists, such as pilocarpine and cevimeline, which enhance the production of saliva and tears (Baer and Walitt, 2018). However, these drugs have cholinergic side effects, such as flushing chills, and excessive sweating (Baer and Walitt, 2018). To prevent this, moisturization of the oral tissues can also be achieved by using artificial saliva (Bayetto and Logan, 2010).

The oral microbiome, being one of the most diverse microbial communities in the human body, plays a crucial role in maintaining human health (Zhou et al., 2023). The human oral microbiome encompasses all microorganisms found in the oral cavity—including distinct habitats such as teeth, gingival sulcus, attached gingiva, tongue, cheek, lip, hard palate, and soft palate—and its contiguous extensions like the tonsils, pharynx, esophagus, Eustachian tube, middle ear, trachea, lungs, nasal passages, and sinuses, though most studies and samples focus on the oral cavity itself (Dewhirst et al., 2010). The oral cavity contains over 700 different species of bacteria, fungi, viruses, archaea, and protozoa. Bacteria are the most extensively studied microorganisms in the oral cavity, yet only 57% of the bacterial species present have been named (Kozak and Pawlik, 2023). In healthy individuals, the oral microbiome predominantly comprises facultative anaerobic Gram-positive bacteria (Kozak and Pawlik, 2023). 16S rDNA profiling of a healthy oral cavity identified six major bacterial phyla: Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria, Bacteroidetes, and Spirochaetes (Verma et al., 2018). Brief descriptions of the more important bacteria are provided below.

One of the most important representatives of Firmicutes is Streptococcus mutans, which lives mainly on tooth surfaces (Lemos et al., 2019; Sedghi et al., 2021). Its ability to metabolize carbohydrates, create low-pH acids and finally produce glucans (an important component for the backbone of dental plaque), which makes it one of the existing etiological factors of caries (Lemos et al., 2019). Actinomyces, belonging to Actinobacteria, are the natural flora of the oral cavity, living on the surfaces of mucous membranes (Könönen and Wade, 2015). They constitute (A. oris, A. naeslundi) quite an important element of the oral biofilm, and may also participate in the development of dental caries (Könönen and Wade, 2015). As a result of the microbiological balance in the oral cavity, there may be a sudden increase in the occurrence of Actinomyces, causing actinomycosis (Smego and Foglia, 1998; Könönen and Wade, 2015). Haemophilus, which belong to the Proteobacteria, cause a wide range of infections that require blood-derived factors for their growth (Musher, 1996). A natural component of the oral cavity is H. aphrophilus, which under specific conditions can cause bacterial endocarditis (Musher, 1996). Porphyromonas gingivalis is an anaerobic gram-negative bacterium, classified as Bacteroidetes, strongly associated with periodontal disease (Zhou and Luo, 2019). By regulating the human’s immune response, it disrupts its chomesotasis, which contributes to the occurrence of gum diseases (Zhou and Luo, 2019). These actions are due to a series of protein adhesins, binding proteinases and hemin. More and more often, you can also find information about the connection between P. gingivalis and the occurrence of cancers, among others. squamous cell carcinoma of the oral cavity or esophagus (Zhou and Luo, 2019). Fusobacterium nucleatum is a Gram-negative rod-shaped bacterium, belonging to Fusobacteria, commonly found in the oral cavity. It plays a crucial role in dental plaque biofilm formation (McIlvanna et al., 2021). Although traditionally not considered pathogenic in the oral cavity, it has emerged as an important player in driving inflammation and may act as an opportunistic pathogen in extra-oral sites (McIlvanna et al., 2021). F. nucleatum acts as a “bridging” bacterium, facilitating interactions between early and late colonizers in dental plaque and has the potential to bind to various cell types, thus contribute to carcinogenesis through its adhesins FadA and Fap2 (McIlvanna et al., 2021). Treponema denticola, belonging to Spirochaetes play a significant role in oral diseases such as periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis (Yousefi et al., 2020). These bacteria contribute to tissue destruction through direct bacterial action and by triggering an exaggerated host inflammatory response (Yousefi et al., 2020).

Bacteria are the primary focus of research on the human oral microbiome and constitute the majority of biomass in the oral environment, whereas fungi are estimated to make up as little as less than 0.1% of it (Baker et al., 2017). The initial study examining the composition of the fungal component oral in healthy individuals’ microbiota found that the most commonly identified fungal genera were Candida, Cladosporium, Aureobasidium, Saccharomycetales, and Aspergillus (Ghannoum et al., 2010). Fungi in the oral cavity have been studied mainly in relation to diseases, and their role in maintaining a healthy oral ecology remains largely unknown (Krom et al., 2014). The review exploring current knowledge on fungi-bacteria interactions likewise highlights the needs for further research to understand fungi’s contribution to oral health (Krom et al., 2014). The oral virome in healthy individuals consists mainly of bacteriophages, which are more numerous than eukaryotic viruses (Baker et al., 2017). Compared to the oral bacteriome, oral virome is characterised by significant individual variability while remaining stable over time (Baker et al., 2017). Despite of technological advancements, studying the human virome is challenging due to the low abundance of viral nucleic acids, the difficulty in purifying unknown virions, and the complexities in analyzing and identifying novel viruses (Bikel et al., 2015). The viruses causing symptoms are well-studied, while the vast, symptomless majority remains poorly understood (Lecuit and Eloit, 2013).

Reduced amount of saliva plays an important role in Sjögren’s syndrome (Bayetto and Logan, 2010; van der Meulen et al., 2018b; Negrini et al., 2022). First, it cleanses the oral cavity - dilutes food remains and washes out bacteria from the surface of the mucous membranes (Lynge Pedersen and Belstrøm, 2019). In SS, the persistence of food and microorganisms is prolonged (sugar clearance is also reduced), which leads to changes in the composition of the flora, promoting the growth of acid-forming and tolerant bacteria. Acidic environment, in particular Streptococcus mutans, Streptococcus sobrinus and Lactobacilli, which produce acids from retained carbohydrates and increase the risk of developing caries (Li et al., 2022). S. mutans may have a close correlation with the occurrence of Candida albicans (Li et al., 2022). Moreover, in a study conducted by Nadig et al., which concerned determining the relationship between salivary flow rate and the number of Candida in xerostomia, a correlation was observed between low SFR and an increase in the number of Candida, in which C. albicans was the most common (Nadig et al., 2017). Analysis of the interactions between these two species showed that protein genes related to carbohydrate metabolism in C. albicans were enhanced (Li et al., 2022). What’s more, as a result of this culture, the mass of the total biofilm increased (Li et al., 2022). Another issue are mucins present in saliva (Lynge Pedersen and Belstrøm, 2019). They prevent the adhesion and formation of a biofilm by microorganisms such as staphylococci, streptococci or Candida and participate in the binding of, for example, Porphyromonas gingivalis (Li et al., 2022). The coating formed from saliva is important in preventing the colonization of various surfaces of the oral cavity (Li et al., 2022). The topic of the role of saliva is very complex. We know that its impact on the microbiome is influenced by among others, salivary amylase, the salivary peroxidation system, salivary lysosomes, lactoferrin, rich proteins in proline, staterin, cystatin, histatin and immunoglobulins (Lynge Pedersen and Belstrøm, 2019). In recent years, many studies have been carried out aiming to describe the differences between the microbiome in people with Sjögren’s syndrome, people with xerostomia for other reasons and healthy patients. In a study by Huang YF et al. statistically significant differences were observed - a decrease in the Bacteroides genus and a significant increase in the Firmicutes genus (Huang et al., 2019). Another study suggests that a high ratio of Firmicutes to Proteobacteria (taco) may be a characteristic indicator of xerostomia (van der Meulen et al., 2018a). In addition, a higher total number of microorganisms of the genus Candida, Streptococcus mutans, lactobacilli was noticed (Myers, 2015). Although impaired salivary secretion has been shown to be the dominant contributor to the change in oral microflora in SS, differences were reported in the microbiota between people with xerostomia and Sjögren’s syndrome (van der Meulen et al., 2018b). Similary, the same that could be used in treatment and diagnosis (Sembler-Møller et al., 2019), however not all studies confirm this. Example of which is a lower relative number of Granulicatella and Bergeyella in patients with compared to Sjögren’s syndrome (van der Meulen et al., 2018a). A study conducted on a small group using PCR methods allowing the division of microorganisms even into their species showed significant differences (Rusthen et al., 2019). First of all, a lower percentage of Streptococci, Neisseria, Actinomyces lingnae and Haemophilus was observed in people with Sjögren’s syndrome, and a higher percentage of Porphyromonas pasteri, Megasphaera micronuciformis (Rusthen et al., 2019). The study’s authors emphasize that their findings may in the future be used to detect SS based on the examination of the oral microbiome as a specific biomarker of the disease, and prove that the changes in oral flora in Sjögren’s syndrome are caused not only by reduced salivary secretion, but also by other factors that have not yet been described (Rusthen et al., 2019). Another publication describes Lactobacillus and Streptococcus as potential biomarkers (Kim et al., 2022). It also suggests that in the future it may be possible to treat the symptoms of Sjögren’s syndrome by using prebiotics, which is already being conducted in the treatment of other autoimmune diseases such as rheumatism (Zamani et al., 2016). Interestingly, there are publications suggesting that changes in the oral microbiome may indirectly lead to the development of Sjögren’s syndrome (Tsigalou et al., 2018). Therefore, monitoring the oral microflora could be more specific in prevention, but the exact pathomechanism of this disease has not yet been clarified (Tsigalou et al., 2018). This is an interesting direction for future research on the links between Sjögren’s syndrome and the oral microbiome (Tsigalou et al., 2018). A comparison of the microbiome in xerostomia with the healthy oral cavity is presented in the Table 1 .

Sjögren’s syndrome often causes decreased salivation – xerostomia (Bayetto and Logan, 2010; Baer and Walitt, 2018). It is estimated that 88% of patients with SS have decreased salivary secretion, which ultimately resulted in xerostomia in around 75-92% of patients (Cartee et al., 2015). These symptoms can be treated with agents that lead to produce more saliva (sugar-free chewing gum, pilocarpine, cevimyelin) or with artificial saliva, which may play a similar role (Bayetto and Logan, 2010). These pharmacological and non-pharmacological agents are described below.

Agents used in the treatment of Sjögren’s syndrome, especially in case of xerostomia, have a real impact on the composition of the oral microbiome. However, some of them, such as pilocarpine, despite providing relief from dry mouth, do not significantly affect the risk of periodontopathy or tooth decay, even though they are considered one of the best means of treating this disease. It should be emphasized that this field is not well discovered. Further research is needed to determine the impact of individual agents, in particular cevimeline, on the oral microbiome. Research on artificial saliva is also necessary due to the general treatment of its effect on xerostomia, without taking into account the division into xerostomia caused by Sjögren’s syndrome, radiotherapy or chemotherapy. This is especially important in the context of the current discussion of similarities and differences in the oral microbiome resulting from the above-mentioned factors.