Since saliva is important for the microbial balance in the mouth, hyposalivation may lead to disturbances of the microbial ecology. Under normal conditions about 0.2–0.4 ml/min of unstimulated saliva is produced. A secretion rate ≤0.1 ml/min is considered to be hyposalivation. Corresponding figures for stimulated whole saliva are 1–3 ml/min and ≤0.7 ml/min. Below are results from studies of the oral microflora both in rinsing samples and in samples collected from specific sites in subjects with hyposalivation of different origins presented.

The oral microflora in subjects undergoing radiation therapy was investigated already in the 1970s [17, 18]. Brown et al. [17] showed a marked increase in numbers of lactobacilli, Candida, and staphylococci and a decrease in Streptococcus sanguinis and Fusobacterium, after completed radiation therapy (RT). These alterations remained 30 months later. Also Llory et al. [18] reported persisting high numbers and proportions of acidogenic microorganisms 1–4 years after completed radiation therapy. In these earlier studies, very low salivary secretion rates, a mean of 0.08 ml/min, were reported in subjects who had undergone radiation therapy in the head and neck region [17]. Since then, cancer treatment has improved markedly with more accurate focusing techniques, the use of three-dimensional planning of the radiation field, brachytherapy (iridium implant in the tumor), intensity modulated radiotherapy and sparing of the parotid glands on the contralateral side. These factors have decreased the negative effects on the salivary glands, and higher salivary secretion rates can be regained compared with those 40–50 years ago. Consequently, radiation therapy may have less pronounced effects on the oral microflora than it used to have.

The oral microflora in subjects with radiation-induced hyposalivation has been investigated also in the latest decades [19–23]. In the study by Almståhl et al. [19], the oral microflora in rinsing samples in groups with hyposalivation of different origins was compared. Compared with subjects with primary Sjögren’s syndrome and subjects with hyposalivation due to medication or of unknown origin, the group with hyposalivation due to radiation therapy (6 months after completed treatment) had the highest numbers and proportions of lactobacilli and Candida albicans. About one third of the patients had very high levels of mutans streptococci, while in one third of the patients, this bacterium was not detected. An increase in salivary numbers of bacteria associated with caries and Candida has also been reported by others [20, 21]. Hu et al. [23] followed the changes in the oral microbiome of patients undergoing radiation therapy. Pooled supragingival plaque from the maxillary first molar was collected before and during radiation therapy and analyzed by pyrosequencing of the 16S rRNA. The variation in species was reduced by radiation therapy. Higher doses of radiation lead to a stronger species reduction. Also a change in bacterial species was observed. Before radiation therapy the most abundant phyla were, in order of prevalence, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. During radiation therapy the order was changed to Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes [23]. Six genera were found in all subjects at the start of the study: Streptococcus, Actinomyces, Capnocytophaga, Neisseria, Granulicatella, and Gemella. Of these, only Streptococcus and Actinomyces were always found in all subjects across the different time points of the therapy.

In a few studies the oral microflora in different ecosystems has been analyzed using cultivation techniques [21, 22]. Al-Nawas and Grötz [21] found no significant changes in the frequencies of bacteria associated with periodontal diseases in the gingival crevice region during the 12 months’ follow-up period after radiation therapy.

In a study by Almståhl et al. [22], the oral microflora in five ecosystems (the dorsum of the tongue, buccal mucosa, vestibulum in the molar region, supragingival plaque, and gingival crevice region) was analyzed. Samples were taken from subjects 6 months after completed radiation therapy (RT group) and compared with the microflora in controls matched according to age, sex, and number of teeth and with normal salivary secretion rate. The cancer patients had received radiation doses ranging between 64.6 and 76.6 Gy, and the major salivary glands were included in the radiation field. Twelve of the 13 subjects in the study were also treated with brachytherapy (between 6 and 30 Gy). The subjects showed severe hyposalivation—the mean unstimulated salivary secretion rate was 0.005 ± 0.02 ml/min (median 0 ml/min) and the mean stimulated secretion rate 0.32 ± 0.32 ml/min (median 0.23 ml/min).

Primary Sjögren’s syndrome (pSS) is as previously mentioned an autoimmune disease directed against glandular tissues. One of the diagnostic criteria is the presence of inflammatory cells in the salivary glands. All secretory glands including the salivary glands are affected. Nine out of ten patients with pSS are women. The oral microflora in subjects with pSS has been analyzed in several studies [19, 24–28]. High levels of mutans streptococci and lactobacilli were reported by both Lundström and Lindström [24] and Kolavic et al. [25]. Also Leung et al. [29] found increased levels of lactobacilli in saliva of patients with Sjögren’s syndrome. Lactobacillus species frequently found were L. acidophilus, L. fermentum, and L. minutus. Candida were detected on the tongue in 59 % of pSS subjects [24]. In the study by Leung et al. [29], also the microflora in supragingival plaque was examined. They found a significantly higher proportion of Lactobacillus species, especially L. acidophilus, compared to controls with normal salivary secretion rate. No significant differences in prevalence, number, or proportion of S. mutans or anaerobic Gram-negative rods were detected. In the study by Almståhl et al. [19], the microflora in rinsing samples from different groups with hyposalivation was examined. The pSS group included showed the second highest level of lactobacilli. Mutans streptococci were detected in 95 % of the subjects in pSS group and mostly in high numbers.

In another study, the microflora in five ecosystems (the dorsum of the tongue, buccal mucosa, vestibulum in the molar region, supragingival plaque, and gingival crevice region) was analyzed in 20 subjects with pSS (≥16 teeth and no removable dentures) and compared with the microflora in matched controls with normal salivary secretion rate [27]. Their unstimulated salivary secretion rate was 0.02 ± 0.02 ml/min (median 0.01 ml/min) and the stimulated salivary secretion rate 0.47 ± 0.38 ml/min median (0.40 ml/min).

On the dorsum of the tongue, the pSS group had a higher proportion of streptococci of the total microbial count and a higher proportion of S. salivarius of the total number of streptococci than the controls, while the proportion of F. nucleatum of the total count was lower. On the buccal mucosa, the pSS group had a higher total microbial count and a higher number of streptococci. In the vestibulum in the molar region, there were no statistically significant differences in the numbers or proportions. In the supragingival plaque, the pSS group showed a significantly higher number and proportion of mutans streptococci compared with the controls. Also the numbers of lactobacilli and C. albicans were significantly higher, and the proportion of lactobacilli tended to be higher. In the gingival crevice region, there were no statistically significant differences in the numbers or proportions of the microorganisms. The periodontal pathogens P. gingivalis and A. actinomycetemcomitans were not detected in any of the pSS subjects. As for the RT group, the most marked change in oral microflora in the pSS group was an increase in acidogenic and aciduric microorganisms, especially in the supragingival plaque.

The knowledge on the oral microflora in subjects with hyposalivation due to medicines is scarce. This might be due to the fact that it is a very heterogenous group. In three studies subjects with hyposalivation due to medicines or of unknown origin were examined [19, 30, 31]. The subjects included in this group had undergone biopsy of the labial minor gland for investigation of a possible Sjögren’s syndrome but had not shown any signs of inflammation. Therefore, they did not get the diagnosis of Sjögren’s syndrome. For some of the patients, medication might explain their hyposalivation. Other possible reasons for their hyposalivation might have been hormonal changes or depression.

In rinsing samples, this group showed increased numbers of lactobacilli compared with subjects with normal salivary secretion rate [19]. However, their levels of lactobacilli were considerably lower than for the subjects with pSS and radiation-induced hyposalivation. This is most likely due to the fact that this group had a much higher stimulated salivary secretion rate, 0.93 ± 0.54 ml/min, compared with the other groups, 0.47 ± 0.38 ml/min in the pSS group and 0.35 ± 0.38 ml/min in the RT group.

As for subjects with radiation-induced hyposalivation and pSS, the microflora in five ecosystems in subjects with hyposalivation of unknown origin was studied [30]. To be included the subjects had ≥16 teeth and no removable dentures and an unstimulated secretion rate of ≤0.1 ml/min. The mean unstimulated secretion rate was 0.04 ± 0.04 ml/min (median 0.04 ml/min) and the stimulated secretion rate 0.98 ± 0.51 ml/min (median 0.97 ml/min).

On the dorsum of the tongue, the hyposalivated group had a lower number of F. nucleatum. On the buccal mucosa, there were no significant differences in the numbers or proportions of microorganisms. In the vestibulum in the molar region, the number of enterococci tended to be higher in the hyposalivated group. In the supragingival plaque, the hyposalivated group had significantly higher numbers of mutans streptococci and lactobacilli and tended to have an increased number of C. albicans, but no significant differences in proportions of microorganisms were detected. In the gingival crevice, no significant differences in the numbers of proportions of microorganisms were detected.

To summarize the findings of the oral microflora in subjects with hyposalivation of different origins, a common feature was an increase in lactobacilli [19, 22, 27, 30]. The most dramatic increase was seen for the RT subjects followed by the pSS subjects. In the RT group the aggressive cancer treatment, rapid decrease in salivary secretion rate, and changed dietary habits during cancer treatment might have influence on the marked increase in lactobacilli. In the pSS subjects a contributing factor to the high levels of lactobacilli might be their high number of filled surfaces and crown joints, which can serve as retention sites for the lactobacilli. For mutans streptococci the differences between the hyposalivated subjects and the controls were not so clear. Mutans streptococci were however more frequently detected in the hyposalivated subjects, and many had high levels. Another interesting finding was that the frequency and number of C. albicans were higher in the interproximal supragingival plaque than on the tongue and mucosal membranes. This stresses the importance of interdental cleaning for subjects with hyposalivation. The group with hyposalivation due to medication or of unknown origin also had increased levels of lactobacilli, but the changes in microflora were not so marked as in the irradiated patients or the patients with Sjögren’s syndrome. It is however possible that subjects with hyposalivation due to medicines or of unknown origin are pre-Sjögren’s syndrome patients and that their salivary secretion rates will gradually decrease and thereby their risk of a disturbed microflora increases.

The subjects included in studies examining the oral microflora in subjects with hyposalivation have been middle aged [19, 22, 27, 28, 31, 32]. A growing group with hyposalivation, mostly due to polypharmacy, are elderly people. The proportion of elderly having natural teeth is increasing. The oral microflora was analyzed in a group of dependent elderly (79–98 years old with ≥10 teeth and no removable prosthesis [33]. Their unstimulated and stimulated salivary secretion rates were not possible to measure, but it can be suspected that it was lower than normal due to the high intake of medicines, mean 6 ± 3 medicines (median 6). The majority of the subjects showed low labial minor gland flow rates. In the supragingival plaque, the dependent elderly showed high numbers and proportions of lactobacilli, mutans streptococci, and Candida, and enterococci were frequently found. This group is a challenge considering that many are not able to maintain a good oral hygiene due to decreased fine motor skills or dementia.

An example of what can happen with the oral microbiome when one is not able to take care of the oral hygiene is patients who are mechanically ventilated in intensive care units. Ten to thirty percent of the mechanically ventilated patients develop pneumonia, and 50 % of the antibiotics prescribed in intensive care units are related to (suspected) ventilator-associated pneumonia [34]. Ventilator-associated pneumonia is the leading cause of death from nosocomial infections in the United States [35]. One of the risk factors for the development of pneumonia is the reduced salivary flow and associated accumulation of dental plaque. The absence of oral stimulation and the use of xerogenic drugs combined with limited or hampered oral care result in the development of a microflora that is potentially pathogenic when entering the lungs. Causative agents of ventilator-associated pneumonia are Gram-negative enteric bacteria such as E. coli and Klebsiella pneumoniae and other species such as Pseudomonas aeruginosa and S. aureus. These species are usually not found in dental plaque. Comparison of dental plaque of patients in intensive care units with that of healthy controls revealed that patients had higher levels of dental plaque and this plaque included respiratory pathogens. In contrast, dental plaque of controls was rarely colonized by respiratory pathogens [36]. Somewhat unexpected is the finding that plaque of patients that recently received antibiotic treatment had a greater chance of being colonized by respiratory pathogens than plaque of those without treatment [37]. Possibly, these patients receive antibiotic treatment because they have a higher risk for developing infections. It is also possible that suppression of the commensal flora by antibiotics gives pathogens an opportunity to multiply. Treatment of these patients consists of oral care by tooth brushing combined with chlorhexidine or povidone-iodine flushing [38, 39].

As mentioned already, many hyposalivated subjects have an increase in mutans streptococci and lactobacilli, which are associated with caries development. The occurrence of caries is the result of “an ecological disaster” as it was called by Philip Marsh [40]. Sucrose is in dental plaque fermented to primarily lactic acid that causes a decrease in pH in dental plaque. A low pH favors the growth of acidophilic bacteria like S. mutans and Lactobacillus spp. which are acidogenic at a pH lower than 4.7. This leads to demineralization of the dental enamel. The decrease in pH is more important than the availability of carbohydrates [41]. Although frequent sucrose consumption is considered the major cause of dental caries, people with hyposalivation are at high risk of developing caries [42]. In caries prediction models, for example, cariogram, saliva secretion is one of the predictive factors for caries experience [43]. Also salivary buffering capacity, which is usually lower in subjects with low saliva secretion, is one of the predictive factors in this model.

Saliva is relatively effective in protection against dental caries. Caries usually develops at sites that are not easily accessible for saliva and not on smooth surfaces. Saliva protects against caries in four ways: