Prevalence of cancer in relation to signs of periodontal inflammation

Funding Information: The study was supported by the Swedish Ministry of Health and Social Affairs (grant F84/ 189) and Karolinska Institutet, Stockholm, Sweden, and by grants from The Finnish Society of Sciences and Letters, the Finnish Medical Society, Finland, and the King Gustav V´s and Queen Victoria’ s Freemason´s Foundation, Sweden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 Meurman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.We investigated the associations between periodontal inflammation (gingivitis and periodontitis) and all-kind malignancies, specifically breast and prostate cancer, in a cohort followed-up for 30 years. The study hypothesis was based on the oral inflammation vs. systemic health paradigm. A sample of 2,168 subjects from an original cohort of 105,718 individuals from the greater Stockholm area in Sweden that had been followed since 1985 was investigated. Swedish national health registers were used in the study. Chi-square tests and logistic multiple regression analyses were conducted. The results showed that periodontitis was significantly associated with any cancer after adjusting for gender, age, income, and education (p = 0.015). The probability of getting cancer increased on average by 38% if the patient had periodontitis vs. had not; the odds ratio was 1.380 (95% confidence interval l.066-1.786). No significant association was observed between periodontitis and breast cancer (p = 0.608), while the association between periodontitis and prostate cancer tended towards significance (p = 0.082). However, no statistically significant difference was found between the observed and the calculated distribution of any cancer in gingivitis groups (p = 0.079). Thus, the study hypothesis was partly confirmed by showing a statistically significant association between periodontitis and any cancer.Peer reviewe

Investigations of a Possible Chemical Effect of Salvadora persica

Salvadora persica is commonly used chewing sticks in many parts of the world as an oral hygiene tool. This study measured the amount of benzyl isothiocyanate (BITC) released into the mouth and assessed its retention time in saliva. The study also tested if the released amount of BITC could potentially be antibacterial or cytotoxic. Twelve subjects brushed their teeth with fresh Miswak once, twice, and four times. The amount of BITC in the saliva and in the used brushes was quantified using gas chromatography-mass spectrometry. The antibacterial effect of BITC and Miswak essential oil (MEO) was tested against Haemophilus influenzae, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis. The cytotoxic effect on gingival fibroblasts and keratinocytes was tested using MTT. The highest amount of the active compounds was detected in saliva after using the Miswak tip for once and immediately. It significantly decreased when the Miswak tip was used more than once and thus after 10 min. The growth of the tested bacteria was inhibited by MEO and BITC in a dose dependent manner, P. gingivalis being the most sensitive. MTT assay showed that BITC and MEO were cytotoxic towards gingival fibroblasts while oral keratinocytes showed resistance. This study suggests that the Miswak tip should be cut before each use to ensure the maximum effect

Mucin 4 and matrix metalloproteinase 7 as novel salivary biomarkers for periodontitis

Aim: Periodontitis is a chronic inflammatory disease, characterized by irreversible destruction of tooth-supporting tissue including alveolar bone. We recently reported mucin 4 ( MUC4) and matrix metalloproteinase 7 (MMP7) as highly associated with periodontitis in gingival tissue biopsies. The aim of this study was to further investigate the levels of MUC4 and MMP7 in saliva and gingival crevicular fluid (GCF) samples of patients with periodontitis. Materials and Methods: Saliva and GCF samples were collected from periodontitis patients and healthy controls. The levels of MUC4, MMP7, and total protein concentrations were analysed using ELISA or Bradford assay. Results: MUC4 levels were significantly lower in saliva and GCF from periodontitis patients relative to healthy controls. MMP7 levels were significantly higher in saliva and GCF from periodontitis patients. Multivariate analysis revealed that MUC4 was significantly associated with periodontitis after adjusting for age and smoking habits and, moreover, that the combination of MUC4 and MMP7 accurately discriminated periodontitis from healthy controls. Conclusions: MUC4 and MMP7 may be utilized as possible novel biomarkers for periodontitis.Peer reviewe

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation

Background: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis. Methods: The presence of Td-CTLP within orodigestive tumour tissues was examined using immunohistochemistry. Oral, tonsillar, and oesophageal squamous cell carcinomas, alongside gastric, pancreatic, and colon adenocarcinomas were stained with a Td-CTLP-specific antibody. Gingival tissue from periodontitis patients served as positive controls. SDS-PAGE and immunoblot were used to analyse the immumodulatory activity of Td-CTLP in vitro. Results: Td-CTLP was present in majority of orodigestive tumour samples. Td-CTLP was found to convert pro MMP-8 and -9 into their active forms. In addition, Td-CTLP was able to degrade the proteinase inhibitors TIMP-1, TIMP-2, and alpha-1-antichymotrypsin, as well as complement C1q. Conclusions: Because of its presence within tumours and regulatory activity on proteins critical for the regulation of tumour microenvironment and inflammation, the Td-CTLP may contribute to orodigestive carcinogenesis.Peer reviewe

Probiotic supplements containing Lactobacillus reuteri does not affect the levels of matrix metalloproteinases and interferons in oral wound healing

Abstract Objective The use of beneficial bacteria may stimulate wound healing. We performed a randomized, placebo-controlled double-blind cross-over study comprising ten healthy volunteers. The aim was to investigate the impact of topical and systemic applications of probiotic lactobacilli (Lactobacillus reuteri) on the healing of standardized wounds (punch biopsies) in the oral mucosa. The expression of selected matrix metalloproteinases (MMP’S) and interferons (IFN’s) was analyzed with multiplex immunoassays in the wound exudate during the first healing week (day 2, 5 and 8). Results All participants completed the study and in all cases, the healing after the punch biopsies was uneventful. The concentrations of MMP-1, MMP-2, MMP-3 decreased with time in both the test- and control group. The MMP levels were consistently lower during the probiotic intervention when compared with placebo but the differences were not statistically significant. Likewise, the concentrations if IFN-alpha2, IFN-beta and IFN-gamma decreased with time with no significant differences between the test and placebo interventions. Within the limitations of this pilot study, we were unable to demonstrate an influence of probiotic supplements containing L. reuteri on the concentrations of selected matrix metalloproteinases and interferons from mucosal wounds within 1 week after a standardized punch biopsy. Trial registration ClinicalTrials.gov Identifier NCT03210779. Date of registration: July 7, 201

Adherence of human oral keratinocytes and gingival fibroblasts to nano-structured titanium surfaces

BACKGROUND: A key element for long-term success of dental implants is integration of the implant surface with the surrounding host tissues. Modification of titanium implant surfaces can enhance osteoblast activity but their effects on soft-tissue cells are unclear. Adherence of human keratinocytes and gingival fibroblasts to control commercially pure titanium (CpTi) and two surfaces prepared by anodic oxidation was therefore investigated. Since implant abutments are exposed to a bacteria-rich environment in vivo, the effect of oral bacteria on keratinocyte adhesion was also evaluated. METHODS: The surfaces were characterized using scanning electron microscopy (SEM). The number of adhered cells and binding strength, as well as vitality of fibroblasts and keratinocytes were evaluated using confocal scanning laser microscopy after staining with Live/Dead Baclight. To evaluate the effect of bacteria on adherence and vitality, keratinocytes were co-cultured with a four-species streptococcal consortium. RESULTS: SEM analysis showed the two anodically oxidized surfaces to be nano-structured with differing degrees of pore-density. Over 24 hours, both fibroblasts and keratinocytes adhered well to the nano-structured surfaces, although to a somewhat lesser degree than to CpTi (range 42-89% of the levels on CpTi). The strength of keratinocyte adhesion was greater than that of the fibroblasts but no differences in adhesion strength could be observed between the two nano-structured surfaces and the CpTi. The consortium of commensal streptococci markedly reduced keratinocyte adherence on all the surfaces as well as compromising membrane integrity of the adhered cells. CONCLUSION: Both the vitality and level of adherence of soft-tissue cells to the nano-structured surfaces was similar to that on CpTi. Co-culture with streptococci reduced the number of keratinocytes on all the surfaces to approximately the same level and caused cell damage, suggesting that commensal bacteria could affect adherence of soft-tissue cells to abutment surfaces in vivo

Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis

This study aimed to investigate the periodontal health of patients with established rheumatoid arthritis (RA) in relation to oral microbiota, systemic and oral inflammatory mediators, and RA disease activity. Forty patients underwent full-mouth dental/periodontal and rheumatological examination, including collection of blood, saliva, gingival crevicular fluid (GCF) and subgingival plaque. Composition of plaque and saliva microbiota were analysed using 16S rRNA sequencing and levels of inflammatory mediators by multiplex-immunoassay. The majority of the patients (75%) had moderate or severe periodontitis and the rest had no/mild periodontitis. Anti-citrullinated protein antibody (ACPA) positivity was significantly more frequent in the moderate/severe periodontitis (86%) compared to the no/mild group (50%). No significance between groups was observed for RA disease duration or activity, or type of medication. Levels of sCD30/TNFRSF8, IFN-2, IL-19, IL-26, MMP-1, gp130/sIL-6R ss, and sTNF-R1 were significantly higher in serum or GCF, and April/TNFSF13 was significantly higher in serum and saliva samples in moderate/severe periodontitis. The microbial composition in plaque also differed significantly between the two groups. In conclusion, the majority of RA patients had moderate/severe periodontitis and that this severe form of the disease was significantly associated with ACPA positivity, an altered subgingival microbial profile, and increased levels of systemic and oral inflammatory mediators