Salivary Biomarkers and Oral Health in Liver Transplant Recipients, with an Emphasis on Diabetes.

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.

Oral mucosal health in liver transplant recipients and controls.

Immunosuppressive drugs and other medications may predispose patients to oral diseases. Data on oral mucosal health in recipients of liver transplantation (LT) are limited. We, therefore, recruited 84 LT recipients (64 with chronic liver disease and 20 with acute liver failure) for clinical oral examinations in a cross-sectional, case-control study. Their oral health had been clinically examined before transplantation. The prevalence of oral mucosal lesions (OMLs) was assessed in groups with different etiologies of liver disease and in groups with different immunosuppressive medications, and these groups were compared to controls selected from a nationwide survey in Finland (n = 252). Risk factors for OMLs were evaluated with logistic regression. OMLs were more frequent in LT recipients versus controls (43% versus 15%, P < 0.001), and the use of steroids raised the prevalence to 53%. Drug-induced gingival overgrowth was the single most common type of lesion, and its prevalence was significantly higher for patients using cyclosporine A (CSA; 29%) versus patients using tacrolimus (TAC; 5%, P = 0.007); the prevalence was even higher with the simultaneous use of calcium channel blockers and CSA (47%) or TAC (8%, P = 0.002). Lesions with malignant potential such as drug-induced lichenoid reactions, oral lichen planus-like lesions, leukoplakias, and ulcers occurred in 13% of the patients with chronic liver disease and in 6% of the controls. Every third patient with chronic liver disease had reduced salivary flow, and more than half of all patients were positive for Candida; this risk was higher with steroids. In conclusion, the high frequency of OMLs among LT recipients can be explained not only by immunosuppressive drugs but also by other medications. Because dry mouth affects oral health and OMLs may have the potential for malignant transformation, annual oral examinations are indicated.

Self-reported oral symptoms and signs in liver transplant recipients and a control population.

Recipients of liver transplantation (LT) receive lifelong immunosuppression, which causes side effects. We investigated self-reported oral symptoms and associated risk factors with the following hypothesis: symptoms and signs would differ between LT recipients of different etiology groups and also between LT recipients and a control population. Eighty-four LT recipients (64 with chronic liver disease and 20 with acute liver disease) were recruited for clinical oral and salivary examinations (median follow-up = 5.7 years). A structured questionnaire was used to record subjective oral symptoms. Matched controls (n = 252) came from the National Finnish Health 2000 survey. The prevalence of symptoms was compared between the groups, and the risk factors for oral symptoms were analyzed. Xerostomia was prevalent in 48.4% of the chronic LT recipients and in 42.1% of the acute LT recipients. This subjective feeling of dry mouth was only partly linked to objectively measured hyposalivation. The chronic transplant recipients had significantly lower unstimulated salivary flow rates than the acute transplant recipients (0.34 ± 0.31 versus 0.61 ± 0.49 mL/minute, P = 0.005). Among the chronic transplant recipients, hyposalivation with unstimulated salivary flow was associated with fewer teeth (17.7 ± 8.2 versus 21.9 ± 8.4, P = 0.047) and more dentures (33.3% versus 12.2%, P = not significant). The chronic patients reported significantly more dysphagia than their controls (23.4% versus 11.5%, P = 0.02). Increases in the number of medications increased the symptoms in all groups. In conclusion, dysphagia was significantly more prevalent among the chronic LT recipients versus the controls. The number of medications was a risk factor for dry mouth-related symptoms for both the LT recipients and the controls. The chronic transplant recipients presented with lower salivary flow rates than the acute transplant recipients. Hyposalivation correlated with generally worse oral health among the chronic transplant recipients. These differences between the chronic and acute LT recipients may have been due to differences in their medical conditions due to the different etiologies.

Oral and dental health care of oral cancer patients: hyposalivation, caries and infections.

Oral cancer and its treatment can cause a variety of problems to patients, also as regards maintaining their daily oral hygiene. Surgery mutilates tissues which may hamper cleaning the teeth and mucosal surfaces. The patient may have complicated reconstructive structures that also need continuous attention. Radiotherapy-induced hyposalivation further complicates the situation and decreases the quality of life. Consequently, dental caries, mucosal diseases such as candidosis and sialadenitis become problematic to treat. Hence every effort should be focused on prevention. In caries prevention intensified fluoride therapy together with dietary counseling is needed. Oral cancer patients also need to be frequently referred to dental hygienists for professional cleaning. Drinking enough daily and moisturizing mucosal surfaces with commercial dry-mouth products, vegetable oils, milk products and respective topical agents need to be individually recommended. In addition, patients with severe dry mouth cases may also benefit from the prescription of pilocarpine tablets. In oral candidosis, the microbiological diagnosis must be confirmed before administration of antifungal drugs in order to avoid the selection pressure to resistant strains.

Molecular and clinical analyses of the gene encoding the collagen-binding adhesin of Streptococcus mutans.

Streptococcus mutans is a known pathogen of dental caries and its major cell surface antigens have been widely investigated. Recently, an approximately 120 kDa Cnm protein with binding properties to type I collagen was identified, and its encoding gene (cnm) cloned and sequenced. In the present study, we sequenced cnm from 47 different clinical S. mutans strains and found that the nucleotide alignment of the collagen-binding domain was well conserved. We devised a PCR method for identifying the cnm gene, examined the prevalence of cnm-positive S. mutans strains in various mother-child groups, and assessed the significance of such strains for transmission and dental caries. The detection rate of cnm-positive strains was significantly lower in strains isolated from Japanese children in the 2000s (8.0 %) as compared to those isolated in the 1980s (15.8 %) (P<0.05). Furthermore, the presence of S. mutans possessing cnm in salivary specimens collected from 55 S. mutans-positive mother-child pairs was 40 and 32.7 % in the mothers and children, respectively. The frequency of cnm-positive children whose mothers were also positive was 72 %, which was significantly higher than that of cnm-positive children with negative mothers (P<0.0001, odds ratio 17.5). In addition, clinical parameters indicating dental caries were significantly increased in children with cnm-positive S. mutans in saliva (n=13), as compared to those with cnm-negative S. mutans (n=15) and S. mutans-negative children (n=20) (P<0.01). These results indicate that cnm-positive S. mutans strains are closely correlated with dental caries, while vertical transmission in cnm-positive mother-child pairs was also demonstrated.

Streptococcus mutans clonal variation revealed by multilocus sequence typing.

Streptococcus mutans is the major pathogen of dental caries, a biofilm-dependent infectious disease, and occasionally causes infective endocarditis. S. mutans strains have been classified into four serotypes (c, e, f, and k). However, little is known about the S. mutans population, including the clonal relationships among strains of S. mutans, in relation to the particular clones that cause systemic diseases. To address this issue, we have developed a multilocus sequence typing (MLST) scheme for S. mutans. Eight housekeeping gene fragments were sequenced from each of 102 S. mutans isolates collected from the four serotypes in Japan and Finland. Between 14 and 23 alleles per locus were identified, allowing us theoretically to distinguish more than 1.2 x 10(10) sequence types. We identified 92 sequence types in these 102 isolates, indicating that S. mutans contains a diverse population. Whereas serotype c strains were widely distributed in the dendrogram, serotype e, f, and k strains were differentiated into clonal complexes. Therefore, we conclude that the ancestral strain of S. mutans was serotype c. No geographic specificity was identified. However, the distribution of the collagen-binding protein gene (cnm) and direct evidence of mother-to-child transmission were clearly evident. In conclusion, the superior discriminatory capacity of this MLST scheme for S. mutans may have important practical implications.

Acetaldehyde production from ethanol by oral streptococci.

Alcohol is a well documented risk factor for upper digestive tract cancers. It has been shown that acetaldehyde, the first metabolite of ethanol is carcinogenic. The role of microbes in the production of acetaldehyde to the oral cavity has previously been described in several studies. In the present study, the aim was to investigate the capability of viridans group streptococci of normal oral flora to produce acetaldehyde in vitro during ethanol incubation. Furthermore, the aim was to measure the alcohol dehydrogenase (ADH) activity of the bacteria. Eight clinical strains and eight American Type Culture Collection (ATCC) strains of viridans group streptococci were selected for the study. Bacterial suspensions were incubated in two different ethanol concentrations, 11 mM and 1100 mM and the acetaldehyde was measured by gas chromatography. ADH-activity was measured by using a sensitive spectroscopy. The results show significant differences between the bacterial strains regarding acetaldehyde production capability and the detected ADH-activity. In particular, clinical strain of Streptococcus salivarius, both clinical and culture collection strains of Streptococcus intermedius and culture collection strain of Streptococcus mitis produced high amounts of acetaldehyde in 11 mM and 1100 mM ethanol incubation. All these four bacterial strains also showed significant ADH-enzyme activity. Twelve other strains were found to be low acetaldehyde producers. Consequently, our study shows that viridans group streptococci may play a role in metabolizing ethanol to carcinogenic acetaldehyde in the mouth. The observation supports the concept of a novel mechanism in the pathogenesis of oral cancer.