Thursday, August 7, 2025

Maple compound offers new way to fight tooth decay

 

 — A new study in the journal Microbiology Spectrum highlights the potential of using a natural compound from maple to combat the bacteria responsible for tooth decay: Streptococcus mutans. The compound, epicatechin gallate, is a powerful and safe alternative to traditional plaque-fighting agents. Its natural abundance, affordability and lack of toxicity make it especially promising for inclusion in oral care products such as mouthwashes, offering a safer option for young children, who often accidentally swallow mouthwash.

The new study emerged as an offshoot of research into natural compounds that inhibit biofilm formation in Listeria monocytogenes, a foodborne pathogen. As is often the case in science, the researchers made an unexpected observation that Listeria readily forms biofilms on plant materials, including most wood, but seems to avoid certain types, especially maple. This piqued the researchers’ curiosity. They isolated polyphenolic compounds from maple that inhibit Listeria attachment and biofilm formation. They also identified their target: sortase A, an enzyme that anchors adhesins to the bacterial cell wall. When sortase A is inhibited, these adhesins are not anchored in the bacterial cell wall, impairing the ability of Listeria to attach to surfaces and form biofilms. That discovery led the researchers to investigate whether similar mechanisms exist in related bacteria. Sortase A in Streptococcus species, which is Listeria’s cousin in the Bacillota phylum, turned out to be quite similar. One species in particular, Streptococcus mutans, stood out because it causes dental caries, commonly known as cavities. 

“Since S. mutans initiates cavities by forming biofilms (plaques) on teeth and producing acid that destroys tooth enamel, we asked: could maple polyphenols also inhibit S. mutans biofilms? That question drove this study,” said corresponding study author Mark Gomelsky, Ph.D., Martha Gilliam Professor of Microbiology and Director of the Microbiology Program at the University of Wyoming.

The researchers first used computer modeling to see whether maple polyphenols could bind to the sortase A enzyme from S. mutans, and discovered that they did. Next, they purified the sortase A in the lab and confirmed that these compounds inhibit its activity in a test tube. Finally, they assessed whether maple polyphenols block S. mutans from forming biofilms on plastic teeth and on hydroxyapatite disks—a stand-in for real tooth enamel— and discovered they worked there too. 

“In a way, this study felt almost too easy. Everything fell into place just as we predicted. That’s a rare experience in science, and probably the first time it’s happened in my 35-year research career,” Gomelsky said. “We discovered that several polyphenols present in maple wood or maple sap can inhibit the sortase enzyme in S. mutans, which in turn prevents this cavity-causing bacterium from attaching to tooth surfaces.” Interestingly, the most potent inhibitor was (-)-epicatechin gallate (ECG), a compound also present in green and black tea, though in much higher amounts in tea than in maple sap. Drinking green tea has long been associated with lower rates of cavities, and its main polyphenol, (-)-epigallocatechin gallate (EGCG), has been used in dental products. The researchers found that EGCG does inhibit S. mutans biofilms, but it’s not nearly as effective as ECG. This raises the intriguing possibility that the moderate effects seen with EGCG-based dental products may be due to using the suboptimal compound, instead of the more potent ECG.

“Our findings suggest that ECG or other edible polyphenols with anti-sortase activity could be added to dental products to help prevent cavities through an antibiofilm mechanism,” Gomelsky said. “This is different from traditional approaches, which rely on killing bacteria with alcohol, disinfectants or essential oils, or on fluoride to remineralize enamel. The antibiofilm approach using edible polyphenols is especially appealing for young children. For example, young children can’t use conventional mouthwashes because they might swallow them and risk toxicity. A safer alternative, such as a mouthwash containing an effective dose of an edible polyphenol, could provide protection without harmful side effects.”

Gomelsky said they are actively developing plant polyphenol-based dental products through a startup founded by University of Wyoming students and the first author of this study, Ahmed Elbakush, Ph.D. 


Wednesday, July 30, 2025

Polygenic architecture of dental caries: single nucleotide polymorphisms in genetic epidemiology

 



Peer-Reviewed Publication

Xia & He Publishing Inc.

Main genetic groups with potential association with dental caries according to genetic pathways 

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The figure illustrates the major categories of genes that may influence susceptibility to dental caries, organized by their biological functions and pathways. These groups include: (1) Enamel formation genes, which play roles in the development and mineralization of the tooth enamel and dentin; (2) Immune response genes, involved in innate and adaptive immune mechanisms that modulate the host response to cariogenic bacteria; (3) Saliva-related genes, which influence the composition, flow, and buffering capacity of saliva, impacting oral microbiota and caries risk; (4) Taste perception genes, which may affect dietary preferences and sugar intake, indirectly influencing caries development; Each group contributes to different aspects of carie

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Credit: Luiz Alexandre Chisini

Dental caries remains a significant global public health burden, affecting billions worldwide despite preventive measures. While behavioral and socioeconomic factors are primary drivers, individual susceptibility varies markedly among those with similar risk profiles. This review synthesizes evidence establishing a substantial genetic component in caries etiology, mediated through polygenic mechanisms and epistatic interactions across key biological pathways.

Genetic Pathways and Key Findings

1. Tooth Mineralization Genes:

  • Key Genes: AMBNAMELXENAMMMPs (e.g., MMP2MMP20), KLK4TFIP11BMP7, *DLX3/DLX4*.

  • Mechanism: Variants alter enamel/dentin structure and mineralization, increasing susceptibility to acid demineralization. Epistatic interactions (e.g., *TUFT1-MMP2-TFIP11*, *MMP2-BMP7*) significantly influence lifelong caries trajectories, often undetected by single-SNP analyses. Meta-analyses confirm associations (e.g., AMELX OR=1.78, TFIP11 OR=1.64).

2. Taste Perception Genes:

  • Key Genes: TAS2R38 (bitter), TAS1R2TAS1R3 (sweet).

  • Mechanism: SNPs (e.g., TAS2R38 rs713598) alter taste sensitivity, influencing sugar preference and intake. The CG genotype of rs713598 is protective (OR=0.35). TAS1R3 rs307355 shows dose-dependent caries risk across life stages, with epistasis between *TAS1R2/TAS1R3*. GWAS consistently implicate TAS2R genes.

3. Salivary Genes:

  • Key Genes: CA6AQP5MUC5B.

  • Mechanism: Variants impact saliva flow, buffering capacity (CA6), and antimicrobial properties (MUC5B). CA6 rs17032907-TT increases risk 3.23-fold; AQP5 variants are protective (OR=0.75). Reduced MUC5B facilitates S. mutans adhesion. GWAS link CA12 (salivary buffering) to caries.

4. Immune Response Genes:

  • Key Genes: MBL2LTFDEFB1.

  • Mechanism: Polymorphisms impair innate immunity (e.g., MBL2 rs11003125-CG/GG), reducing antimicrobial action against cariogenic biofilms. Pooled MBL2 SNPs increase risk (homozygote OR=2.12; heterozygote OR=2.22).

Genome-Wide vs. Candidate Gene Studies

  • GWAS identified novel loci (AJAP1ADAMTS3ISL1BCOR) beyond traditional pathways, implicating odontogenesis, neural function, and immune regulation. Taste (TAS2R) and mineralization (*DLX3/DLX4*) pathways were validated.

  • Limited Overlap: Discrepancies arise from GWAS' stringent significance thresholds, phenotypic heterogeneity (DMFT vs. ICDAS), population stratification, and inadequate power/corrections in candidate studies.

Critical Methodological Challenges

  1. Population Stratification: Inadequate control for genetic ancestry confounds associations. Self-reported race is insufficient; genomic control (e.g., PCA) is essential.

  2. Hardy-Weinberg Equilibrium (HWE): Deviations may indicate genotyping errors or bias; pre-analysis HWE checks are crucial.

  3. Linkage Disequilibrium (LD): Failure to account for LD biases epistasis and association results.

  4. Multiple Testing: Bonferroni corrections are fundamental but rarely applied, inflating false positives (e.g., only 17% of candidate studies corrected adequately).

  5. Epistasis: Single-SNP analyses overlook complex interactions; advanced models (e.g., polygenic risk scores) are needed.

Conclusions and Future Directions

Dental caries is a polygenic trait shaped by interactions across enamel integrity, taste preference, salivary function, and immunity. Future studies must:

  • Employ larger, diverse cohorts with standardized phenotyping.

  • Integrate epistasis, gene-environment interactions, and polygenic risk scores.

  • Rigorously address ancestry, LD, HWE, and multiple testing.

  • Prioritize translational applications, such as genetic panels for high-risk identification and personalized prevention.

 

Full text

https://www.xiahepublishing.com/1555-3884/GE-2025-00018


Cannabis use disorder triples risk of oral cancer


Peer-Reviewed Publication

University of California - San Diego

A recent study by researchers at the University of California San Diego School of Medicine has found that individuals with cannabis use disorder (CUD) are more than three times more likely to develop oral cancer within five years compared to those without CUD. The study highlights the potential long-term health risks associated with problematic cannabis use.

In 2022, 17.7 million people reported daily or near-daily cannabis use. Though CUD requires a formal diagnosis and not all cannabis users develop the disorder, recent research suggests that as many as 3 in 10 cannabis users will develop CUD.

As cannabis becomes more widely available and socially accepted, it is essential to understand its potential health risks. While many consider cannabis to be safer than other drugs, such as tobacco and alcohol, there are still many unknowns about the health impacts of cannabis, particularly how the drug influences cancer risk. The new study sought to determine the relationship between CUD and oral cancer, for which tobacco smoking is known to be a significant risk factor.

“Cannabis smoke contains many of the same carcinogenic compounds found in tobacco smoke, which have known damaging effects on the epithelial tissue that lines the mouth," said Raphael Cuomo, Ph.D. associate professor in the Department of Anesthesiology at UC San Diego School of Medicine and member of UC San Diego Moores Cancer Center. "These findings add to a growing body of evidence suggesting that chronic or problematic cannabis use may contribute to cancer risk in tissues exposed to combustion products."

By analyzing the electronic health records from over 45,000 patients, of whom 949 developed CUD, Cuomo found:

  • After adjusting for age, sex, body mass index and smoking status, people had a 325 percent  times higher likelihood of contracting oral cancer within five years compared to those without CUD.
  • Tobacco smokers with CUD were 624 percent more likely to contract oral cancer within five years compared to tobacco smokers without CUD.

Because the association between CUD and oral cancer remained even after controlling for smoking status, and because CUD was associated with greater oral cancer risk even when the analysis was restricted to smokers, the researchers hypothesize that there may be other factors underlying this risk in addition to smoke inhalation. For example, THC, the active compound in cannabis is known to have immune-suppressing effects, which may contribute to increased cancer risk.

While more research is needed to fully explain the association between cannabis and oral cancer, the study's results have immediate implications for cancer screening practices and public health messaging. In particular, the findings emphasize the need for further research on the long-term effects of cannabis use and the importance of integrating oral health awareness into substance use disorder treatment and counseling.

The study, published online in Preventive Medicine Reports, reported no external funding or conflicts of interest. 

Tuesday, July 29, 2025

Why you may get future vaccines via dental floss

 


Peer-Reviewed Publication

North Carolina State University

Using dental floss to introduce vaccine 

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Researchers have demonstrated a novel vaccine delivery method in an animal model, using dental floss to introduce vaccine via the tissue between the teeth and gums. The testing found that the new technique stimulates the production of antibodies in mucosal surfaces, such as the lining of the nose and lungs. 

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Credit: Jie Sun, NC State University

Researchers have demonstrated a novel vaccine delivery method in an animal model, using dental floss to introduce vaccine via the tissue between the teeth and gums. The testing found that the new technique stimulates the production of antibodies in mucosal surfaces, such as the lining of the nose and lungs.

“Mucosal surfaces are important, because they are a source of entry for pathogens, such as influenza and COVID,” says Harvinder Singh Gill, corresponding author of a paper on the work. “However, if a vaccine is given by injection, antibodies are primarily produced in the bloodstream throughout the body, and relatively few antibodies are produced on mucosal surfaces.

“But we know that when a vaccine is given via the mucosal surface, antibodies are stimulated not only in the bloodstream, but also on mucosal surfaces,” says Gill, who is the Ronald B. and Cynthia J. McNeill Term Professor in Nanomedicine at North Carolina State University. “This improves the body’s ability to prevent infection, because there is an additional line of antibody defense before a pathogen enters the body.”

This is where the junctional epithelium comes in. The term epithelium applies to the tissue that lines the surface of your body parts, such as the lining of your lungs, stomach and intestines. Most epithelial tissues include robust barriers that are designed to keep bad things – from viruses to dirt – from entering your blood stream. But the junctional epithelium is different.

The junctional epithelium is a thin layer of tissue located in the deepest part of the pocket between the tooth and the gum, and it lacks the barrier features found in other epithelial tissues. The lack of a barrier allows the junctional epithelium to release immune cells to fight bacteria – you find these immune cells in your saliva, as well as between your teeth and gums.

“Because the junctional epithelium is more permeable than other epithelial tissues – and is a mucosal layer – it presents a unique opportunity for introducing vaccines to the body in a way that will stimulate enhanced antibody production across the body’s mucosal layers,” says Gill.

To determine the viability of delivering vaccines via the junctional epithelium, the researchers applied vaccine to unwaxed dental floss and then flossed the teeth of lab mice. Specifically, the researchers compared antibody production in mice that received a peptide flu vaccine via flossing the junctional epithelium; via the nasal epithelium; or via placing vaccine on the mucosal tissue under the tongue.

“We found that applying vaccine via the junctional epithelium produces far superior antibody response on mucosal surfaces than the current gold standard for vaccinating via the oral cavity, which involves placing vaccine under the tongue,” says Rohan Ingrole, first author of the paper, who was a Ph.D. student under Gill at Texas Tech University. “The flossing technique also provides comparable protection against flu virus as compared to the vaccine being given via the nasal epithelium.”

“This is extremely promising, because most vaccine formulations cannot be given via the nasal epithelium – the barrier features in that mucosal surface prevent efficient uptake of the vaccine,” Gill says. “Intranasal delivery also has the potential to cause the vaccine to reach the brain, which can pose safety concerns. However, vaccination via the junctional epithelium offers no such risk. For this experiment, we chose one of the few vaccine formulations that actually works for nasal delivery because we wanted to see how junctional epithelium delivery compared to the best-case scenario for nasal delivery.”

The researchers also tested whether the junctional epithelium delivery method worked for three other prominent classes of vaccines: proteins, inactivated viruses and mRNA. In all three cases, the epithelial junction delivery technique produced robust antibody responses in the bloodstream and across mucosal surfaces.

The researchers also found that, at least in the animal model, it didn’t matter whether food and water were consumed immediately after flossing with the vaccine – the immune response was the same.

But while regular floss serves as an adequate vaccine delivery method for lab mice, the researchers know it’s not practical to ask people to hold vaccine-coated floss in their fingers. To address that challenge the researchers used a floss pick. A floss pick consists of a piece of floss stretched between two prongs that can be held by a handle.

Specifically, the researchers coated the floss in floss picks with fluorescent food dye. The researchers then recruited 27 study participants, explained the concept of applying vaccine via floss, and asked the participants to try to deposit the food dye in their epithelial junction with a floss pick.

“We found that approximately 60% of the dye was deposited in the gum pocket, which suggests that floss picks may be a practical vaccine delivery method to the epithelial junction,” Ingrole says.

“We’re optimistic about that work and – depending on our findings – may then move toward clinical trials,” Gill says.

While there are still many questions that need to be answered before the floss technique can be considered for clinical use, the researchers think there could be significant advantages beyond the improved antibody response on mucosal surfaces.

“For example, it would be easy to administer, and it addresses concerns many people have about being vaccinated with needles,” Gill says. “And we think this technique should be comparable in price to other vaccine delivery techniques.

There are also some drawbacks. For example, this technique would not work on infants and toddlers who do not yet have teeth.

“In addition, we would need to know more about how or whether this approach would work for people who have gum disease or other oral infections,” Gill says.

The paper, “Floss-based vaccination targets the gingival sulcus for mucosal and systemic immunization,” is published in the journal Nature Biomedical Engineering. Co-authors of the paper include Akhilesh Kumar Shakya, Chang Hyun Lee and Lazar Nesovic of Texas Tech; Gaurav Joshi of Texas Tech and NC State; and Richard Compans of Emory University.

The study was supported in part by the National Institutes of Health (NIH) under grants R01AI137846 and R01DE033759, and by funds from the Whitacre Endowed Chair in Science and Engineering at Texas Tech University.

Gill, Ingrole and Shakya are co-inventors on a patent related to targeting the junctional epithelium for vaccination.

Saturday, July 26, 2025

Transforming implant success: How gum tissue expert consensus may change dentistry

 


Decision tree of PIKM augmentation at second-stage surgerye. 

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Decision tree of PIKM augmentation at second-stage surgerye.

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Credit: International Journal of Oral Science


Long-term success of dental implants depends not just on bone integration but also on the health of surrounding gum tissue. Yet, gum augmentation practices often vary, leading to inconsistent outcomes. A new expert consensus offers standardized surgical guidelines for enhancing keratinized mucosa (KM) during second-stage implant surgery—a key moment when soft tissue can be managed before prosthetics are placed. The study evaluates commonly used procedures, including flap repositioning, grafting, and synthetic materials, to help clinicians choose the right approach for each patient. This consensus marks a turning point in soft tissue management, aiming to reduce complications, improve aesthetics, and ensure lasting implant stability.

Dental implants have revolutionized oral rehabilitation, but their longevity depends on more than just a strong anchor in bone. The soft tissue that surrounds the implant—specifically the band of keratinized mucosa (KM) —acts as a barrier against bacteria and mechanical stress. When this tissue is too narrow, patients face higher risks of inflammation, discomfort, and tissue breakdown. Despite the development of several surgical methods for KM augmentation, clinicians face confusion due to differing techniques and unclear protocols. These inconsistencies, combined with growing patient expectations, highlight a clear need: to define evidence-based, practical strategies for regenerating this critical tissue zone.

In June 2025, a multidisciplinary team of oral health experts across China released a consensus report (DOI: 10.1038/s41368-025-00379-3) in the International Journal of Oral Science on optimizing peri-implant keratinized mucosa (PIKM) augmentation. Led by Sichuan University, the report synthesizes clinical data and surgical experience to offer standardized recommendations for soft tissue management during second-stage implant procedures. By clarifying when and how to use methods such as apically repositioned flaps (ARF), free gingival grafts (FGG), and soft tissue substitutes, the consensus provides clinicians with a decision-making roadmap to improve long-term implant outcomes.

The expert group assessed four mainstream surgical techniques—ARF, FGG, SFGG, and soft tissue substitutes—detailing their indications, benefits, and drawbacks. FGG remains the gold standard, reliably increasing KM width and thickness, but at the cost of significant donor site trauma and esthetic mismatches. ARF offers a less invasive alternative with good color integration but depends heavily on existing tissue. SFGG, involving thin strips of grafted tissue, reduces donor morbidity and improves aesthetics when combined with collagen matrices, though it is more technique-sensitive.

The consensus also introduces a decision tree to guide surgeons based on implant location, residual KM width, and patient preferences. For example, FGG is advised in cases with <2 mm of KM, especially in the lower jaw. ARF is suited for the upper back teeth, while aesthetic concerns in the front teeth call for SFGG with tissue substitutes. Factors such as gingival thickness, surgical experience, and cost are also considered. The result is a practical clinical tool for tailoring surgeries to individual needs, helping ensure both biological health and cosmetic satisfaction.

“Soft tissue is the unsung hero of implant dentistry,” says Prof. Quan Yuan and Dr. Shiwen Zhang, lead authors of the consensus. “For years, we focused mainly on bone integration, but healthy gum tissue is equally essential for long-term implant success. This report offers a unified guide based on evidence and clinical wisdom, helping clinicians make informed, patient-centered decisions. With clearer strategies, we can now deliver not just function but also comfort and beauty.”

This consensus fills a critical gap in implant dentistry, offering clinicians a clear and adaptable framework for soft tissue regeneration. It promotes consistency in treatment planning, streamlines surgical decision-making, and aligns procedures with both patient expectations and anatomical realities. Beyond immediate clinical impact, the report sets the stage for future innovation. Researchers are encouraged to develop biomaterials that balance predictability with esthetics, and to pursue long-term trials to validate outcomes. Digital imaging, tissue engineering, and individualized care models will likely play central roles in the next wave of implant success stories—stories that begin with the right soft tissue foundation.

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References

DOI

10.1038/s41368-025-00379-3

Original Source URL

https://doi.org/10.1038/s41368-025-00379-3