lactoferrin and Dental-Caries

This meta-analysis evaluated the association of LTF, ENAM, and AMELX polymorphisms with dental caries susceptibility.. We searched the Scopus, PubMed/Medline, Web of Science, and Cochrane Library databases to retrieve articles published by October 2019. Review Manager 5.3 software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The results of publication bias tests were retrieved by Comprehensive Meta-Analysis 2.0 software.. A total of 150 relevant records were identified; out of which, 16 were entered into the analysis (4 studies assessed LTF, 11 ENAM, and 11 AMELX polymorphisms). Of all polymorphisms, there was a significant association only between ENAM rs3796704 polymorphism and dental caries susceptibility. Both ENAM rs3796704 and AMELX rs17878486 polymorphisms had a significant association with dental caries risk in the Caucasian ethnicity and the studies including caries-free control group.. The results of this meta-analysis showed that the G allele and the GG genotype of ENAM rs3796704 were associated with an increased risk of caries in the case group compared with the control group. But there was no association between LTF rs1126478, ENAM (rs1264848 and rs3796703), and AMELX (rs946252, rs17878486, and rs2106416) polymorphisms and dental caries susceptibility.

Topics: Amelogenin; Dental Caries; Dental Caries Susceptibility; Extracellular Matrix Proteins; Genetic Predisposition to Disease; Genotype; Humans; Lactoferrin; Polymorphism, Single Nucleotide

The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results.. A systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants in LTF and the risk of dental caries. We adopted the subsequent inclusion criteria to assess study eligibility: 1) The studies were based on human subjects; 2) the presence of dental caries should be screened for in both the case group and the control group; and 3) genotype data on variants in LTF were available in both the case group and the control group. We calculated odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by using random-effects models to assess the association of genetic variants in LTF with the risk of dental caries. We also performed a gene-based analysis to explore the joint association of multiple genetic variants in LTF with the risk of dental caries.. Our systematic literature search identified six relevant papers for analysis. We found no significant association between rs1126478 and the risk of dental caries when meta-analysing the genotype distribution between subjects with dental caries and those without dental caries (additive model: OR = 1.41; 95% CI = 0.98-2.02; P = 0.065). However, further analysis indicated that rs1126478 was associated with dental risk in subjects who had moderate or severe dental caries compared to those without dental caries (P < 0.0001). The gene-based analysis indicated that multiple genetic variants in LTF were jointly associated with the risk of dental caries (P = 0.002).. The present meta-analysis revealed some evidence of the association between rs1126478 and dental caries and that multiple genetic variants in LTF are jointly associated with the risk of dental caries. Our findings need to be validated by larger studies that adjust for important confounding factors for the risk of dental caries.

Topics: Alleles; Computational Biology; Dental Caries; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Lactoferrin; Male; Models, Genetic; Odds Ratio; Publication Bias; Risk Assessment

The oral cavity harbors different taxonomic groups, the evolutionary coexistence of which develops the oral ecosystem. These resident microorganisms can alter the balance between the physiologic and pathologic conditions that affect the host, both locally and systemically. This highly sophisticated nature of the oral cavity poses a significant therapeutic challenge. Numerous human and animal studies have been conducted to potentiate the efficacy and competence of current treatments of pathologic conditions as well as to develop novel therapeutic modalities. One of these studies is the use of the potent antimicrobial agent lactoferrin (LF), which was originally derived from the host immune system. LF is an 80-kDa glycoprotein that has a free iron sequestration mechanism with evident antimicrobial, anti-tumor, and immunomodulatory properties. A wide range of active peptides have been isolated from the N-terminal region of LF, which possess antimicrobial activities. In this review, we discuss the role of LF and LF-derived peptides under a heterogeneous group of oral and maxillofacial conditions, including bacterial, fungal, viral infections; head and neck cancers; xerostomia; and implantology-bone-related manifestations.

Topics: Animals; Bacteria; Candida albicans; Carcinogenesis; Dental Caries; Humans; Lactoferrin; Mouth Neoplasms; Peptides; Periodontal Diseases; Polymorphism, Single Nucleotide; Streptococcus mutans; Virus Physiological Phenomena

Lactoferrin is one of a number of multifunctional proteins that are present in or on all mucosal surfaces throughout the body. Levels of lactoferrin are consistently elevated in inflammatory diseases such as arthritis, inflammatory bowel diseases, corneal disease, and periodontitis. Single-nucleotide polymorphisms (SNPs) in lactoferrin have been shown to be present in individuals susceptible to Escherichia coli-induced travelers' diarrhea and in tear fluid derived from virally associated corneal disease. Here, we review data showing a lactoferrin SNP in amino acid position 29 in the antimicrobial region of lactoferrin that acts against caries associated bacteria. This SNP was initially discovered in African American subjects with localized aggressive periodontitis (LAP) who had proximal bone loss but minimal proximal caries. Results were confirmed in a genetic association study of children from Brazil with this same SNP who showed a reduced level of caries. In vitro data indicate that lactoferrin from whole saliva derived from subjects with this SNP, recombinant human lactoferrin containing this SNP, or an 11-mer peptide designed for this SNP kills mutans streptococci associated with caries by >1 log. In contrast, the SNP has minimal effect on Gram-negative species associated with periodontitis. Moreover, periodontally healthy subjects homozygous for this lysine (K) SNP have lactoferrin in their saliva that kills mutans streptococci and have reduced proximal decay. The review summarizes data supporting the ecologic plaque hypothesis and suggests that a genetic variant in lactoferrin with K in position 29 when found in saliva and crevice fluid can influence community biofilm composition. We propose that, for caries, this SNP is ethnicity independent and protective by directly killing caries-provoking bacteria (reducing proximal decay). However, the clinical effect of this SNP in LAP is ethnicity dependent, destructive (increases LAP incidence), and complex with mechanisms still to be determined.

Topics: Aggressive Periodontitis; Anti-Infective Agents; Biofilms; Dental Caries; Dental Plaque; Humans; Lactoferrin; Lysine; Polymorphism, Single Nucleotide; Streptococcus mutans

Many antimicrobial agents in human saliva are known to have bacteriostatic or bactericidal effects on cariogenic bacteria, in particular against Streptococcus mutans. Studies have usually been conducted with purified agents (proteins) in vitro. Very little proof exists to show that they also affect oral cariogenic flora in vivo. Recent studies have shown that some salivary systems can act synergistically against Streptococcus mutans. Such synergistic antibacterial activity is likely to exist in the human mouth. Attempts to enhance the anticariogenic properties of saliva have been made by adding antimicrobial proteins such as peroxidase, lactoferrin and lysozyme to oral health products. Although clinical evidence is still limited, the idea of using such antimicrobial agents--"natural antibiotics"--rather than synthetic agents against cariogenic bacteria seems promising.

Topics: Dental Caries; Lactoferrin; Muramidase; Peroxidases; Saliva; Salivary Proteins and Peptides; Streptococcus mutans

A variety of components provide salivary secretions with an array of potentially effective means of combating cariogenic challenges. These defense factors range from a laissez-faire mechanical cleansing to exquisitely controlled production of highly specific antibodies. In between the two extremes are antibacterial systems whose operating characteristics are only beginning to be understood. These systems are well worth our attention. They may be the key to our understanding of variations in individual susceptibility, and could provide valuable leads for development of anticaries agents.

Topics: Adsorption; Agglutination; Animals; Bacteria; Cell Adhesion; Cell Aggregation; Dental Caries; Dental Enamel Solubility; Dental Plaque; Humans; Hydrogen-Ion Concentration; Hydroxyapatites; Lactoferrin; Lactoperoxidase; Muramidase; Saliva; Secretory Rate

In this study, the abundance of the protective salivary proteins lysozyme, lactoferrin, and cystatin S was quantified in the in situ formed pellicle of caries-free and caries-active children to determine whether they may be possible biomarkers for caries.. Pellicle formation was performed in situ for 10 min on ceramic specimens from the oral cavity of children (5-8 years) with caries (n = 17) and without evidence of caries (n = 17). Additionally, unstimulated saliva was collected. Levels of lysozyme, lactoferrin, and cystatin S were measured in desorbed pellicle eluates and saliva using ELISA.. No statistically significant differences were found in the occurrence of cystatin S and lysozyme in saliva and pellicle between caries-active and caries-free children. However, significantly higher amounts of lactoferrin were detected in the pellicle of caries-active children.. The protective salivary protein lactoferrin may be a biomarker for caries susceptibility in children.

Topics: Child; Dental Caries; Dental Pellicle; Humans; Lactoferrin; Muramidase; Saliva; Salivary Proteins and Peptides

Streptococcus mutans is a key pathogen involved in the development of caries lesions. Previously, we developed a novel lactotransferrin-derived antimicrobial peptide LF-1 with potential selective activity against S. mutans. This study aimed to further confirm the selectivity of LF-1 by investigating its effect on S. mutans membrane.. The effects of LF-1 on the viability of human gingival fibroblasts (HGFs) and three common oral Streptococcus (S. mutans, S. sanguinis, and S. gordonii) were evaluated and its structural characteristics were analysed using eukaryotic and prokaryotic membrane-simulated liposomes. Membrane affinity of LF-1 to the three streptococci strains was evaluated using the 3',3'-dipropylthiadicarbocyanine iodide experiment, hydrophobicity assay, and flow cytometry analysis. Transmission electron microscopy (TEM) was used to observe morphological changes in the three streptococcal membranes after LF-1 treatment.. LF-1 displayed lower cytotoxicity to HGFs and selective antibacterial activity against S. mutans. LF-1 exhibited a typical α-helix structure and showed a tryptophan fluorescence blue shift in the prokaryotic membrane-simulated model. The most notable LF-1 induced changes occurred in the membrane potential and hydrophobicity of S. mutans among the three streptococci strains. Furthermore, the fluorescence of fluorescein isothiocyanate-labelled LF-1 was higher in S. mutans than in the other species. TEM showed that 16 μmol/L LF-1 could induce mesosome-like structures in S. mutans, whereas no significant morphological changes occurred in the other species.. LF-1 has selective affinity for and antibacterial activity against S. mutans with strong membrane disrupting ability, highlighting the potential of LF-1 as a crucial antibacterial agent in caries prevention.

Topics: Anti-Bacterial Agents; Antimicrobial Peptides; Biofilms; Dental Caries; Humans; Lactoferrin; Streptococcus; Streptococcus mutans

Tooth decay is one of the most common diseases that humans face during their lifetime. Streptococcus mutans is one of the most critical factors of early tooth decay. These bacteria may produce biofilms in the mouth, which are more resistant to antimicrobial agents. Streptococcus mutans may also demineralize tooth enamel by producing lactic acid. In this study, the effect of nanoliposomes containing lactoferrin at three different concentrations (1·5, 3 and 6 mg ml

Topics: Anti-Infective Agents; Biofilms; Cariostatic Agents; Dental Caries; Humans; Lactic Acid; Lactoferrin; Streptococcus mutans

The present study was conducted to evaluate the antimicrobial effects of the recombinant chimer present in the lactoferrampin-lactoferricin [LFA-LFC] derived from the camel milk on some oral bacteria responsible for dental caries and endodontic failures.. The antimicrobial activity was assessed on the Streptococcus mutans [ATCC 35668], Streptococcus salivarius [ATCC 9222], Streptococcus oralis [ATCC 35037], and Enterococcus faecalis [ATCC 29212], using the microbroth dilution method. The cytotoxicity analysis was done through the MTT method on the human gingival fibroblasts. The data were reported using the descriptive methods and were analyzed by the one-way analysis of variance (ANOVA) and Tukey HSD test.. Results showed that the chimeric peptide had the highest bacteriostatic effect on S. salivarius with the lowest minimum inhibitory concentration value of 1.22 μg/Ml. Also, LFA-LFC chimer was more effective against S. mutans and S. salivarius compared to using 0.2% chlorhexidine mouthwash. The minimum bactericidal concentration analysis showed the most bactericidal effect against S. mutans [1.256 μg/mL]. In spite of the greater antibacterial effect on the evaluated streptococci, this peptide showed lower bacteriostatic and bactericidal properties against E. faecalis compared to the chlorhexidine. Based on cytotoxicity assay, over 50% of the cells were viable in all the evaluation times, demonstrating the biocompatibility of the peptide.. The LFA-LFC chimer revealed comparable or even more effective antibacterial properties compared to the chlorhexidine mouthwash against the caries-inducing bacteria with no toxicity on the human gingival fibroblast cells. So, this peptide can be used as a safe alternative to chlorhexidine and other chemicals in dental applications for the prevention and management of dental caries.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Peptides; Camelus; Dental Caries; Lactoferrin; Microbial Sensitivity Tests; Milk; Peptide Fragments; Streptococcus mutans

This study was conducted to evaluate the antimicrobial potential of the antimicrobial peptides (AMP) LL-37 and human Lactoferricin (LfcinH) on the planktonic growth and biofilm formation of oral pathogenic anaerobes related to caries and periodontitis. Multi-species bacterial suspensions of either facultative anaerobic bacteria (FAB: Streptococcus mutans, Streptococcus sanguinis, Actinomyces naeslundii) or obligate anaerobic bacteria (OAB: Veillonella parvula, Parvimonas micra, Fusobacterium nucleatum) were incubated with different concentrations of AMP solutions for 8 h. Planktonic growth was registered with an ATP-based cell viability assay for FAB and via plate counting for OAB. Biofilms were grown on ZrO

Topics: Antimicrobial Cationic Peptides; Bacteria, Anaerobic; Biofilms; Cathelicidins; Dental Caries; Humans; Lactoferrin; Microbial Sensitivity Tests; Microbial Viability; Oxygen; Periodontal Diseases; Periodontitis

With the development of human genomics, the genetic factors associated with dental caries have receiving increasing attention. This study was performed to evaluate the relationship between lactoferrin (. This prospective case-control study included 360 unrelated children (aged 12-15 years) who received oral health examinations and questionnaire surveys. The children were divided into two groups by counting the numbers of decayed, missing, and filled teeth (DMFT/dmft): case group (n = 162, DMFT/dmft ≥ 1) and control group (n = 198, DMFT/dmft = 0); non-invasive saliva samples were collected to extract genomic DNA. Six SNPs (. The study included 360 individuals with (85 boys and 77 girls) and without a history of caries (96 boys and 102 girls). There were no statistically significant differences in alleles and genotypes among the six SNPs between the two groups.. There is no evidence that polymorphisms of

Topics: Adolescent; Case-Control Studies; Child; China; Dental Caries; Dental Caries Susceptibility; DMF Index; Female; Humans; Lactoferrin; Male; Mannose-Binding Lectin; Mannose-Binding Lectins; Polymorphism, Single Nucleotide; Prospective Studies

Dental caries is related to cariogenic bacteria, salivary components, oral hygiene and host susceptibility. Lactoferrin is an important antimicrobial glycoprotein in saliva; however, the role of the LTF gene in caries susceptibility is unclear. We investigated the association between LTF polymorphisms and the severity of caries.. Our study included 910 healthy paediatric subjects (aged 24-48 months) categorised into three groups: 403 with no caries or white-spot lesions; 230 with moderate caries (8 ≤ dmft ≤ 12); and 277 with severe caries (13 ≤ dmft ≤ 20). Information regarding the subjects' oral habits was gathered using questionnaires. The LTF rs1126477 and rs1126478 polymorphism alleles were genotyped by Sanger sequencing.. The three groups showed no significant differences in LTF polymorphisms alleles, genotypes or haplotypes distribution. Multifactor dimensionality reduction analysis showed that the interactions between breastfeeding for a duration >24 months, night feeding >24 months and high frequency of sweet food intake increased the risk of caries (p = 0.0014); however, we detected no interaction effect between the LTF polymorphisms and oral habits on caries susceptibility.. The LTF rs1126477 and rs1126478 polymorphisms showed no association with the different levels of caries risk in our Chinese paediatric cohort.

Topics: Child, Preschool; Dental Caries; Female; Genetic Predisposition to Disease; Humans; Lactoferrin; Male; Polymorphism, Genetic; Severity of Illness Index; Tooth, Deciduous

The aim of this study was to assess the role of ENAM rs3796703, LTF rs1126478, and TNF-α rs1800629 in high caries susceptibility.. The present case-control study included 1005 unrelated children under 4 years old: 505 with severe caries (dmft index ≥4) and 500 who were caries-free (dmft index=0 and without white-spot lesions). Questionnaires were obtained from parents and gardians about the children's diet and oral behavioural habits. All the children received dental examinations and oral swabbing for human genomic DNA collection. ENAM rs3796703, LTF rs1126478, and TNF-α rs1800629 were genotyped by Sanger sequencing.. The frequency of the ENAM rs3796703T allele (6.7% in the caries group and 4.2% in the caries-free group), CT genotype (12.7% in the caries group and 8.4% in the caries-free group), TNF-α rs1800629 A allele (4.8% in the caries group and 6.8% in the caries-free group), and AG genotype (8.7% in the caries group and 13.2% in the caries-free group) were significantly different between the caries and caries-free groups (p<0.05). No significant difference was found in the LTF rs1126478 allele frequency and genotype distribution between the two groups. The ENAM rs3796703 CT genotype increased caries susceptibility by 60.9% compared to the CC genotype (β=0.746, OR=1.609), and the TNF-α rs1800629 AG genotype reduced caries susceptibility by 47.4% compared to the GG genotype (β=-0.642, OR=0.526). In terms of habits covariates, prolongation of night feeding time by 1 month increased caries susceptibility by 3.3% (β=0.033, OR=1.033); additionally, sweets and acidic drinks consumption 1-2 times per day increased caries susceptibility by 218.2% (β=1.158, OR=3.182), and consumption 3 or more times pe/r day increased susceptibility by 883.5% (β=2.286, OR=9.835) compared to non-consumption. Topical fluoride application decreased caries susceptibility by 43.0% (β=-0.562, OR=0.570).. The ENAM and TNF-α genes are likely associated with caries experience in Chinese children. The ENAM rs3796703 CT genotype might be involved in caries susceptibility, while TNF-α rs1800629 AG genotype might be involved in caries protection.

Topics: Alleles; Child, Preschool; China; Dental Caries; Dental Enamel Proteins; Female; Genetic Predisposition to Disease; Genotype; Humans; Lactoferrin; Male; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha

The objective of this study is to evaluate the importance of human lactoferrin (hLF) in an experimental caries induced by Streptococcus mutans in a lactoferrin-knockout (LFKO(-/-)) mouse model compared with C576J/BL wild-type (WT) mice.. The WT and LFKO(-/-) mice were infected with S. mutans (1 × 10(8) cells) and/or sham infection. Furthermore, the effect of hLF administration was evaluated in LFKO(-/-) mice infected with S. mutans. Mice were assessed for colonization, salivary pH, and caries development.. The results showed that the lactoferrin-knockout infected (LFKO(-/-) I) mice had significantly higher colonization with S. mutans (P = 0.02), lower salivary pH (P = 0.01), and more carious lesions (P = 0.01) when compared to wild-type infected (WTI) mice. In addition, the administration of hLF did not show any evidence of S. mutans colonization as well as carious lesions (P = 0.001) in LFKO(-/-) I mice when compared to untreated LFKO(-/-) I mice.. These results show that endogenous LF protects against S. mutans-induced caries and that exogenous hLF can exert a protective effect against caries development.

Topics: Animals; Anti-Infective Agents; Dental Caries; Humans; Hydrogen-Ion Concentration; Lactoferrin; Male; Mice; Mice, Knockout; Saliva; Streptococcal Infections; Streptococcus mutans

Early childhood caries (ECC) is a chronic, infectious disease that affects the primary dentition of young children. It is the result of an imbalance of risk factors and protective factors that influence the disease. The aim of this study was to assess genetic and environmental factors that may contribute to ECC. Two hundred and fifty-nine unrelated children were evaluated using a cross-sectional design. Data on oral habits were obtained through a questionnaire, and caries experience data were collected by clinical examination. Twenty-three markers in 10 genes were studied. Genotyping of the selected polymorphisms was carried out by real-time PCR. Regression analyses were performed comparing individuals with and without caries experience. Of 259 subjects, 123 were caries free. The genotype TT in ALOX15 (rs7217186) was a risk factor for ECC, whereas the genotypes GG in ENAM (rs1264848), AG and GG in KLK4 (rs198968), CT in LTF (rs4547741), and GG in TUFT1 (rs3790506) were protective for EEC. In conclusion, environmental factors and gene interactions can act as protective or risk factors for ECC. These factors together contribute to the presence and severity of the disease.

Topics: Adenine; Amelogenesis; Arachidonate 15-Lipoxygenase; Child, Preschool; Cross-Sectional Studies; Cytosine; Dental Caries; Dental Enamel Proteins; Epistasis, Genetic; Extracellular Matrix Proteins; Feeding Behavior; Female; Gene-Environment Interaction; Genes, MHC Class II; Genetic Markers; Genetic Variation; Guanine; Humans; Kallikreins; Lactoferrin; Male; Polymorphism, Genetic; Thymine

Dental caries is a common multifactorial disease, resulting from the interaction of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF) is a main salivary glycoprotein, which modulates the host immune-inflammatory and antibacterial response. Although a genetic component for caries outcome has been identified, little is known over the genetic aspects underlying its susceptibility. Thus, the aim of this study was to investigate the association between LTF polymorphisms and caries susceptibility. Six hundred seventy seven 12-year-old students were selected: 346 with (DMFT ≥ 1) and 331 without caries experience (DMFT = 0). Also, individuals concentrating higher levels of disease (polarization group, DMFT ≥ 2, n = 253) were tested against those with DMFT ≤ 1 (n = 424). Along with clinical parameters, three representative LTF tag SNPs (rs6441989, rs2073495, rs11716497) were genotyped and the results were evaluated using univariate and multivariate analyses. Allele A for tag SNP rs6441989 was found to be significantly less frequent in the polarization group, conferring a protective effect against caries experience [AA + AG × GG (OR: 0.710, 95% CI: 0.514-0.980, p = 0.045)], and remained significantly associated with caries protection in the presence of gingivitis (p = 0.020) and plaque (p = 0.035). These results might contribute to the understanding of the genetic control of caries susceptibility in humans.

Topics: Adenine; Buffers; Child; Cytosine; Dental Caries; Dental Caries Susceptibility; Dental Plaque Index; DMF Index; Female; Fluorosis, Dental; Gene Frequency; Genotype; Gingivitis; Guanine; Humans; Hydrogen-Ion Concentration; Lactoferrin; Male; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Saliva; Secretory Rate

Dental caries is a complex, multifactorial disease and one of the most common illnesses worldwide. Its etiology is related to microbial, dietary and host factors. Recent evidence suggests a role of lactotransferrin (LTF) in caries. The purpose of this study was to determine the association between LTF gene polymorphism and dental caries.. In this case-control study, 637 unrelated children, aged 11-13 years, were enrolled. The subjects were divided into two groups, i.e. caries-free (decayed/missing/filled teeth = 0) and caries-affected children (decayed/missing/filled teeth ≥ 1). The LTF rs1126478 (140A/G in exon 2, Lys/Arg) genotypes were determined by PCR with restriction analysis using the EarI enzyme.. Of 637 children, 155 (24.3%) were caries free. There were no statistically significant differences between caries levels and allele or genotype distributions in the total cohort. When the caries-affected group (n = 482) was stratified into low (decayed/missing/filled teeth = 1), moderate (2 ≤ decayed/missing/filled teeth ≤ 3) and high (decayed/missing/filled teeth ≥ 4) caries experience, allele and genotype frequencies were similar among all subgroups.. The LTF 140A/G (exon 2, Lys/Arg) polymorphism was not associated with the susceptibility to or severity of dental caries in the Czech population.

Topics: Adenine; Adolescent; Arginine; Case-Control Studies; Child; Cohort Studies; Czech Republic; Dental Calculus; Dental Caries; Dental Caries Susceptibility; Dental Plaque Index; DMF Index; Exons; Female; Gene Frequency; Genotype; Guanine; Humans; Lactoferrin; Lysine; Male; Periodontal Index; Polymorphism, Genetic

Secretion of antimicrobial proteins (AMPs) and salivary antibodies can modify biofilm formation at host body surfaces. In adolescents, associations have been reported between dental caries and salivary AMPs. AMPs demonstrate direct antimicrobial effects at high concentrations, and at lower more physiological concentrations they mediate changes in host cell defenses, which may alter the local environment and indirectly shape local biofilm formation. The expression of salivary AMPs in preschool children, at an age when the oral bacteria are known to change, has not been investigated. We sought to investigate salivary AMP expression in the context of previously well-documented changes in the oral cavities of this age group including salivary immunoglobulin A (IgA), oral bacteria and dental caries. Dental plaque and saliva were collected from 57 children aged 12-24 months at baseline, of whom 23 children were followed-up at 3 years of age. At each time, saliva was assessed for LL37, human neutrophil peptides 1-3, calprotectin, lactoferrin, salivary IgA, total plaque bacteria and Streptococcus mutans. Over time, concentrations of AMPs, S. mutans and bacteria-specific salivary IgA increased. Caries experience was also recorded when children were 3 years old. Concentrations of AMPs were highest in the saliva of 3-year-old children with the greatest burden of S. mutans. These data suggest that salivary AMPs are variable over time and between individuals, and are linked with bacterial colonization. At follow up, the majority of children remained caries free. Larger longitudinal studies are required to confirm whether salivary AMP levels are predictive of caries and whether their modulation offers therapeutic benefit.

Topics: alpha-Defensins; Antimicrobial Cationic Peptides; Bacterial Load; Biofilms; Cathelicidins; Child, Preschool; Dental Caries; Dental Plaque; Female; Follow-Up Studies; Humans; Immunoglobulin A, Secretory; Infant; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Mouth; Saliva; Salivary Proteins and Peptides; Streptococcus; Streptococcus mutans

Streptococcus mutans is prominently linked to dental caries. Saliva's influence on caries is incompletely understood. Our goal was to identify a salivary protein with anti-S. mutans activity, characterize its genotype, and determine genotypic variants associated with S. mutans activity and reduced caries. An S. mutans affinity column was used to isolate active moieties from saliva obtained from a subject with minimal caries. The bound and eluted protein was identified as lactotransferrin (LTF) by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis and confirmed by Western blotting with LTF antibody. A single nucleotide polymorphism (SNP) that produced a shift from arginine (R) to lysine (K) at amino acid position 47 in the LTF antimicrobial region (rs: 1126478) killed S. mutans in vitro. Saliva from a subject with moderate caries and with the LTF "wild-type" R form at position 47 had no such activity. A pilot genetic study (n = 30) showed that KK subjects were more likely to have anti-S. mutans activity than RR subjects (P = 0.001; relative risk = 3.6; 95% confidence interval [95% CI] = 1.5 to 11.13). Pretreatment of KK saliva with antibody to LTF reduced S. mutans killing in a dose-dependent manner (P = 0.02). KK subjects were less likely to have caries (P = 0.02). A synthetic 11-mer LTF/K peptide killed S. mutans and other caries-related bacteria, while the LTF/R peptide had no effect (P = 0.01). Our results provide functional evidence that the LTF/K variant results in both anti-S. mutans activity and reduced decay. We suggest that the LTF/K variant can influence oral microbial ecology in general and caries-provoking microbes specifically.

Topics: Analysis of Variance; Anti-Infective Agents; Dental Caries; Dental Caries Susceptibility; Genetic Predisposition to Disease; Genotype; Humans; Lactoferrin; Lysine; Polymorphism, Single Nucleotide; Saliva; Streptococcus mutans

To explore the relationship between the concentrations of lactoferrin and lysozyme in saliva and dental caries in primary dentition among Chinese children.. Forty children with high dmft score (dmft > or = 5) and 40 caries-free children (dmft = 0) were sampled and assigned into two groups. Total salivary proteins was measured by means of bicinchoninic acid. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was performed to analyze the images of target straps. Lactoferrin and lysozyme were detected using Western blotting method.. The total salivary protein in high dmft group [(852.02 +/- 206.14) mg/L] was lower than that of caries-free group [(1032.44 +/- 221.99) mg/L, P < 0.001]. The ratio of 77,000 protein in high dmft group [(12.50 +/- 7.73) IA/microg] was significantly higher than that of the caries-free children [(8.71 +/- 4.28) IA/microg, P = 0.009], while there was no significant difference for 14,500 protein between them (P = 0.137). The ratio of lactoferrin was higher in high dmft group [(229.04 +/- 197.14) IA/microg] than that in caries-free children [(144.07 +/- 99.91) IA/microg, P = 0.018], while no significant difference for lysozyme between the two groups (P = 0.091).. Saliva protein is closely related to caries in primary dentition. Lactoferrin may be one of the important components.

Topics: Case-Control Studies; Child, Preschool; Dental Caries; Female; Humans; Lactoferrin; Male; Muramidase; Prevalence; Saliva; Salivary Proteins and Peptides; Tooth, Deciduous

In the present study, a proteomic approach was applied to evaluate the influence of salivary protein composition on in vitro dental pellicle formation and its possible correlation with dental caries. Whole saliva, collected from caries-free and caries-susceptible subjects, was analyzed by two-dimensional electrophoresis, and protein spots were identified by mass spectrometry. Data analysis of salivary protein composition showed a statistically significant correlation between the quantity of acidic proline-rich proteins (PRPs), lipocalin, cystatin SN and cystatin S, and samples from the caries-free group of subjects [decayed, missing or filled teeth (DMFT) = 0]. Samples from subjects with a high DMFT index appear to be correlated with high levels of amylase, immunoglobulin A, and lactoferrin. In vitro pellicle-composition experiments showed the same correlations found for whole saliva. As cystatins are known physiological inhibitors of cathepsins, the higher quantities of lipocalin, and cystatins S and SN found in the samples from the caries-free subjects suggest that inhibition of proteolytic events on other salivary proteins may indirectly provide tooth protection. The correlation between higher levels of the phosphorylated acidic PRPs 1/2 with samples from the caries-free group also suggests a protective role for these proteins.

Topics: Adolescent; Adult; Amylases; Carrier Proteins; Cystatins; Cysteine Proteinase Inhibitors; Dental Caries; Dental Caries Susceptibility; Dental Pellicle; DMF Index; Electrophoresis, Gel, Two-Dimensional; Humans; Immunoglobulin A, Secretory; Lactoferrin; Lipocalin 1; Male; Mass Spectrometry; Peptides; Phosphoproteins; Proline; Proline-Rich Protein Domains; Proteome; Salivary Cystatins; Salivary Proteins and Peptides

Caries as a multifactorial process is influenced by salivary defense. Cluster analyses should give additional information on the role of salivary variables in relation to caries increment.. Samples of unstimulated and stimulated whole saliva from 28 young adults (mean age 23.5+/-2.1 years) were analyzed for flow rate, pH and buffer variables, lysozyme, lactoferrin, peroxidase, thiocyanate, secretory immunoglobulin A, and total protein. The decayed, missing, and filled surfaces (DMFS) were recorded at baseline and after 4 years. Cluster analyses were executed on the basis of salivary data.. The mean caries increment (DeltaDMFS) over 4 years was 6.7+/-4.0 (range 1-16). In two-cluster processing, three out of four volunteers with low caries increments were grouped into one cluster. Only a few variables proved to be important for cluster characteristics.. The results suggest that over 4 years (1) the volunteers with very low caries increment (DeltaDMFS=1) are classified always together, (2) these volunteers do not form a separate cluster by themselves, (3) low caries increment was related to higher salivary flow rate and lower levels of lysozyme and lactoferrin for unstimulated saliva and (4) the partial pressure of CO(2) was of importance in stimulated saliva.

Topics: Adult; Buffers; Carbon Dioxide; Cluster Analysis; Dental Caries; DMF Index; Female; Humans; Hydrogen-Ion Concentration; Immunoglobulin A, Secretory; Incidence; Lactoferrin; Longitudinal Studies; Male; Muramidase; Partial Pressure; Saliva; Salivary Proteins and Peptides; Secretory Rate; Thiocyanates

A group of 15-year-olds were clinically examined for general state of dentition and level of dental caries. Unstimulated whole saliva from the subjects was laboratory tested to determine the levels of lactoferrin, Secretory IgA (SIgA) and alpha1 proteinase inhibitor. A significant relationship was found between the decayed surface index and the levels of lactoferrin, SIgA and alpha1 proteinase inhibitor in the unstimulated saliva. The decayed surface index rose with increases in the levels of lactoferrin, SIgA and alpha1 proteinase inhibitor, the relationship with alpha1 proteinase inhibitor being strongest.

Topics: Adolescent; alpha 1-Antitrypsin; Analysis of Variance; Dental Caries; Dental Plaque Index; DMF Index; Female; Humans; Immunoglobulin A, Secretory; Lactoferrin; Least-Squares Analysis; Linear Models; Male; Oral Hygiene Index; Regression Analysis; Saliva; Salivary Proteins and Peptides; Secretory Rate; Serine Proteinase Inhibitors; Statistics, Nonparametric

Four groups of rats were inoculated with Streptococcus sobrinus ATCC 33478 and fed a cariogenic diet for 42 days. Topical treatment with either distilled water, sodium fluoride (0.2%), a solution containing lactoferrin and lactoperoxidase, or a solution containing liposome-encapsulated lactoferrin and liposome-encapsulated lactoperoxidase was applied at intervals for 35 days. Caries incidence in groups treated with liposome-encapsulated lactoferrin and lactoperoxidase was significantly lower than in control groups. The number of viable Strep. sobrinus and the proportion of Strep. sobrinus in the total counts were significantly higher in liposome-treated groups. Free lactoferrin and lactoperoxidase did not cause a significant reduction in caries incidence.

Topics: Administration, Oral; Administration, Topical; Analysis of Variance; Animals; Cariostatic Agents; Colony Count, Microbial; Dental Caries; Diet, Cariogenic; Disease Models, Animal; Drug Carriers; Incidence; Lactoferrin; Lactoperoxidase; Liposomes; Mouth; Placebos; Random Allocation; Rats; Sodium Fluoride; Streptococcus; Streptococcus mutans; Streptococcus sobrinus

Previous studies of the possible associations of salivary antimicrobial agents with dental caries have given controversial results, obviously mainly because almost all studies have been cross-sectional. Our aim was to find out, in a two-year longitudinal follow-up study, the associations among selected salivary non-immune and immune antimicrobial variables, cariogenic bacteria, and caries increment. The study population was comprised of 63 subjects, all of whom had their 13th birthday during the first study year. In addition to a comprehensive dental examination at baseline and after 2 yrs, paraffin-stimulated whole saliva samples were collected in a standardized way at six-month intervals. Saliva samples were analyzed for flow rate, buffer effect, lysozyme, lactoferrin, total peroxidase activity, hypothiocyanite, thiocyanate, agglutination rate, and total and specific anti-S. mutans IgA and IgG, as well as for numbers of total and mutans streptococci, lactobacilli, and total anaerobic bacteria. Cluster analysis and Spearman-Rank correlation coefficients were used to explore possible associations between and among the studied variables. During the two-year period, a statistically significant increase was observed in flow rate, thiocyanate, agglutination rate, anti-S. mutans IgA antibodies, lactobacilli, and total anaerobes, whereas lysozyme, lactoferrin, and total and anti-S. mutans IgG antibodies declined significantly. Based on various analyses, it can be concluded that, at baseline, total IgG and hypothiocyanite had an inverse relationship with subsequent two-year caries increment, anti-S. mutans IgG antibodies increased with caries development, and mutans streptococci and lactobacilli correlated positively with both baseline caries and caries increment. Total anaerobic microflora was consistently more abundant among caries-free individuals. In spite of the above associations, we conclude that none of the single antimicrobial agents as such has sufficiently strong power to have diagnostic significance in vivo with respect to future caries.

Topics: Adolescent; Agglutination; Anti-Bacterial Agents; Antibodies, Bacterial; Bacteria, Anaerobic; Buffers; Child; Cluster Analysis; Cohort Studies; Colony Count, Microbial; Cross-Sectional Studies; Dental Caries; DMF Index; Female; Finland; Follow-Up Studies; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Lactobacillus; Lactoferrin; Longitudinal Studies; Male; Muramidase; Peroxidases; Saliva; Secretory Rate; Streptococcus mutans; Thiocyanates

The aim was to study the level of salivary proteins with antimicrobial properties in persons with Crohn's disease. Twenty-five patients were recruited, 13 with ongoing symptoms (acute group) and 12 free of clinical signs of the disease at the time of the investigation (nonacute group). A control group matched to the nonacute group was also included in the study. Unstimulated and stimulated whole saliva samples were collected, and the secretion rates estimated. Unstimulated saliva was analyzed for concentrations of total protein, peroxidase, thiocyanate, slgA, lactoferrin, lysozyme, and for specific bacteria aggregation ability. Numbers of mutans streptococci and lactobacilli in saliva were determined, and dental caries status was examined. No differences were found among the groups regarding salivary flow rate, total protein, or any of the antimicrobial proteins. However, three patients with Crohn's disease had no detectable slgA in saliva compared with none in the control group. The lactobacillus count and the number of decayed tooth surfaces were higher in the nonacute group than in the control group.

Topics: Adult; Aged; Case-Control Studies; Colony Count, Microbial; Crohn Disease; Dental Caries; Dental Caries Susceptibility; DMF Index; Female; Humans; Immunity, Innate; Immunoglobulin A, Secretory; Lactobacillus; Lactoferrin; Male; Middle Aged; Muramidase; Peroxidases; Prevalence; Risk Factors; Saliva; Salivary Proteins and Peptides; Salivation; Secretory Rate; Streptococcus mutans

The possible association between salivary non-immunoglobulin (lysozyme, lactoferrin, hypothiocyanite, agglutinins) or immunoglobulin (total IgA, anti-Streptococcus mutans IgA) antimicrobial factors, and the prevalence of dental caries was studied in 59 young adults. These antimicrobial factors were also analysed in relation to the salivary levels of mutans streptococci (MS). The amount of MS correlated significantly (+0.31, p less than 0.05) with the number of initial caries lesions (Di) but not with other caries indices (DMFT, DMFS, DS). The group with no Di (N = 17) had significantly (p less than 0.05) more hypothiocyanite (HOSCN/OSCN-) and anti-S. mutans IgA antibodies in whole saliva than those with initial caries lesions (N = 42). None of the antimicrobial factors alone showed any significant association with salivary MS counts. Our results suggest that HOSCN/OSCN- and anti-S. mutans IgA may be involved in the prevention of the early phases of dental caries.

Topics: Adult; Agglutinins; Anti-Bacterial Agents; Antibodies, Bacterial; Colony Count, Microbial; Dental Caries; DMF Index; Female; Humans; Immunoglobulin A, Secretory; Lactoferrin; Male; Saliva; Salivary Proteins and Peptides; Streptococcus mutans; Thiocyanates

Topics: Bacteria; Dental Caries; Humans; Lactoferrin; Lactoperoxidase; Saliva

1) Certain selective IgA-deficient subjects are capable of synthesizing functional secretory antibodies (s-IgM or s-IgA class) to indigenous oral microorganisms. 2) The presence or absence of these secretory antibodies in saliva can be correlated with the extent of caries involvement. 3) Lysozyme activity is significantly increased in saliva from immune deficient subjects though no correlation can be made with caries experience.

Topics: Agammaglobulinemia; Dental Caries; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin M; Lactoferrin; Muramidase; Parotid Gland; Saliva; Submandibular Gland

Topics: Amylases; Calcium; Dental Caries; Fluorides; Kallikreins; Lactoferrin; Macromolecular Substances; Muramidase; Peroxidases; Phosphorus; Proteins; Saliva; Salivary Glands; Salivation; Secretory Component; Secretory Rate

The mouth harbors organisms in great abundance; yet their variety is limited and it is noteworthy that some species present in the mouth are not found elsewhere. There are many antibacterial substances in the mouth, some of which may contribute to the control of the microbial flora in the mouth. The activity of some is enhanced in the presence of specific antibody, e.g. lactoferrin, although others appear unaffected, e.g. lactoperoxidase. Opinions differ as to whether the level of immunoglobulins in human saliva can be related to caries. Although it has been established in principle that caries can be prevented in animals by means of vaccination, substantial work remains to be done before a vaccine will be available for testing in humans.

Topics: Animals; Antibodies; Bacteriolysis; Cricetinae; Dental Caries; Dental Caries Susceptibility; Haplorhini; Humans; Immunoglobulins; Infant, Newborn; Lactoferrin; Mouth Mucosa; Muramidase; Peroxidases; Rats; Saliva; Vaccination