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Objectives: Periodontitis is associated with Fusobacterium nucleatum (F.n) infection. Although the colonization of renal tissue by F.n is well documented, its specific role in kidney disease has yet to be determined. This study aimed to investigate the potential association between F.n-induced periodontitis and renal interstitial fibrosis., Methods: The rat gingival sulcus was injected with F.n suspension, while the control group (NC) was injected with PBS. The levels of total protein (TP), albumin (ALB), creatinine, and urea nitrogen (BUN) in rat serum and/or urine were quantified using the appropriate kits. Renal interstitial fibrosis and epithelial-mesenchymal transition (EMT) were evaluated in rats using Masson staining, Periodic Schiff-Methenamine (PASM) staining, and immunohistochemical staining. The levels of fibrosis- and EMT-related proteins and the TGF-β/SMAD2/3 and β-catenin signaling pathways were determined using Western blot analysis. F.n in the kidney tissues was quantitatively determined using bacterial 16S rRNA technology., Results: Serum levels of TP, ALB, creatinine, and BUN were not significantly decreased in F.n-infected rats with periodontitis. The levels of creatinine and ALB in the urine were not statistically different between two groups. Masson and PASM staining showed that F.n-induced periodontitis could promote renal interstitial fibrosis in rats. The levels of collagen I, fibronectin (FN), vimentin, and α-SMA were upregulated in the kidney tissues of rats with F.n-induced periodontitis and in F.n-treated HK-2 cells. However, E-cadherin levels were reduced. F.n promoted renal interstitial and HK-2 cell fibrosis in rats by modulating the TGF-β/SMAD2/3 and β-catenin signaling pathways. F.n colonization increased renal interstitial fibrosis in rats., Conclusion: F.n-induced periodontitis promoted EMT by activating the TGF-β/SMAD2/3 and β-catenin signaling pathways, thus promoting renal interstitial fibrosis in rats., Competing Interests: Declaration of competing interest The author declares that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Periodontitis is a chronic inflammatory oral disease that impaired the tooth-supporting apparatus, including gingival tissue destruction and alveolar bone resorption. The initiation of periodontitis is linked to the presence of oral bacteria, particularly P. gingivalis within pathogenic biofilms. Here, we demonstrated the central role of the autophagy regulator Transcription Factor EB (TFEB) in orchestrating autophagy activation and modulating the host immune response against P. gingivalis in periodontitis. Upregulation of TFEB expression at the protein level and heightened nuclear localization occurred during the progressive stages of periodontitis. Functionally, TFEB overexpression emerges as a potent alleviator of periodontitis-associated phenotypes, operating through the activation of autophagy and the inhibition of the NF-κB pathway in both in vivo and in vitro models. In addition, TFEB knockdown exacerbates the inflammatory response by upregulating pro-inflammatory cytokines. The dual regulatory role of TFEB in governing both autophagy and inflammatory responses unveils novel insights into periodontitis pathogenesis, positioning TFEB as a promising therapeutic target for periodontitis intervention., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To describe the microbiological composition of subgingival dental plaque and molecular profile of gingival crevicular fluid (GCF) of periodontal furcation-involved defects., Materials and Methods: Fifty-seven participants with periodontitis contributed with a degree II-III furcation involvement (FI), a non-furcation (NF) periodontal defect and a periodontally healthy site (HS). Subgingival plaque was analysed by sequencing the V3-V4 region of the 16S rRNA gene, and a multiplex bead immunoassay was carried out to estimate the GCF levels of 18 GCF biomarkers. Aiming to explore inherent patterns and the intrinsic structure of data, an AI-clustering method was also applied., Results: In total, 171 subgingival plaque and 84 GCF samples were analysed. Four microbiome clusters were identified and associated with FI, NF and HS. A reduced aerobic microbiota (p = .01) was detected in FI compared with NF; IL-6, MMP-3, MMP-8, BMP-2, SOST, EGF and TIMP-1 levels were increased in the GCF of FI compared with NF., Conclusions: This is the first study to profile periodontal furcation defects from a microbiological and inflammatory standpoint using conventional and AI-based analyses. A reduced aerobic microbial biofilm and an increase of several inflammatory, connective tissue degradation and repair markers were detected compared with other periodontal defects., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Porphyromonas gingivalis, a major pathogen in periodontitis, produces KGP (Lys-gingipain), a cysteine protease that enhances bacterial virulence by promoting tissue invasion and immune evasion. Recent studies highlight microRNAs' role in viral latency, potentially affecting lytic replication through host mechanisms. Herpes virus (HSV) establishes latency via interactions between microRNA-6 (miRH-6) and the ICP4 transcription factor in neural ganglia. This suggests a potential link between periodontitis and HSV-induced latency. This study aims to identify and validate the insilico inhibitory interaction of P. gingivalis KGP with ICP4 transcripts and correlate the presence of viral latency-associated transcript micro-RNA-6 with periodontitis., Methods: Computational docking analysis was performed to investigate the potential interaction between ICP4 and KGP gingipain. The binding energy and RMSD ligand values were calculated to determine the interaction's strength. Ten patients with recurrent clinical attachment loss despite conventional therapy were included in the clinical study. Subgingival tissue samples were collected post-phase I therapy, and HSV microRNA-6 presence was detected via polymerase chain reaction and confirmed through gel electrophoresis., Results: Computational docking identified the ICP4-KGP gingipain complex with the lowest binding energy (-288.29 kJ mol^1) and an RMSD ligand of 1.5 Angstroms, indicating strong interaction potential. Gel electrophoresis confirmed miRH-6 presence in all samples., Conclusion: The identification of miRNA-6 in periodontitis patients and the strong interaction potential between P. gingivalis KGP gingipain and ICP4 transcripts indicate a possible link between bacterial virulence factors and viral latency dynamics in periodontal tissues. These results highlight the complex interplay between oral pathogens, viral microRNAs, and host immune responses in periodontitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yadalam 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.)

The global aging population has led to a rise in age-related health issues, such as malnutrition, metabolic disorders, and even immune decline. Among these concerns, periodontitis holds particular significance for the well-being of the elderly. This study aimed to investigate the impact of aging on inflammatory resorption of alveolar bone in mice with periodontitis, with a specific focus on alterations in the intestinal microenvironment. To achieve this, we established a D-galactose (D-gal)-induced aging mouse model with periodontitis and employed histopathological staining, oxidative stress, and inflammatory factors analyses to assess the severity of periodontitis and the health status. Additionally, the 16S rRNA sequencing and untargeted metabolomics analysis were employed to investigate alterations in the intestinal microbiota and metabolites. Our results showed that D-gal-induced aging mice with periodontitis experienced more pronounced alveolar bone inflammatory resorption and disruptions in the gut barrier, accompanied by an overall decline in physical condition. The microbial composition and structure of aged mice also underwent significant modifications, with a decreased Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, metabolomics analysis demonstrated that D-gal-induced aging primarily influenced lipids and lipid-like molecules metabolism, and enrichment observed in the rheumatoid arthritis and histidine metabolism pathways. These findings provide further evidence that the aging process exacerbates age-related alveolar bone loss (ABL) through disturbances in intestinal homeostasis., (© 2024. The Author(s).)

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted delivery and controlled release of therapeutics. However, the rapid responsiveness to ROS and sustained release of antibacterial drugs are often limited by the challenging microenvironment of periodontitis. Integrating ROS-responsive drug delivery systems with photocatalytic technologies presents a strategic approach to overcome these limitations. Herein, a pillararene-embedded covalent organic framework (PCOF) incorporating the antibacterial prodrug thioacetal (TA) has been developed to treat periodontitis. This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the self-amplifying ROS property to enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity and ROS generation capabilities when employed as drug carriers. When exposed to ROS, TA within the nanoplatform was activated and cleaved into cinnamaldehyde (CA), a highly potent antibacterial compound. By leveraging visible light to activate the site-specific infection targeting, TA-loaded PCOF effectively alleviated periodontitis, thereby advancing the field of antibacterial drug delivery systems.

Irreversible alveolar bone resorption is one of the important clinical manifestations of periodontitis, which is initiated by a plaque biofilm and exacerbated by the imbalance of osteoclast activity and osteogenesis, affecting a patient's masticatory function and resulting in a high recurrence rate of periodontitis. Herein, to reestablish bone homeostasis in periodontitis, a minocycline hydrochloride (MH)-loaded glycopeptide hydrogel (MH/GRW gel ) is fabricated to mediate alveolar bone absorption through sequential antibacterial and RANKL-blocking activities. GRW gel shows an ECM-like fibrous and porous microstructure serving as a scaffold for cell proliferation and differentiation and holds the merits including injectability, self-healing properties, and good biocompatibility. After injection in situ, MH is released rapidly from the hydrogel in the early stage, demonstrating a potent antimicrobial effect to combat the biofilm in the deep periodontal pocket. Moreover, MH/GRW gel exhibits a high specific binding efficiency with RANKL to suppress osteoclast maturation by shielding the RANKL/RANK interaction and enhancing osteogenic differentiation, thereby synergistically regulating bone homeostasis. In the rat periodontitis model, MH/GRW gel significantly curtails periodontitis progression through antimicrobial activity, inhibition of alveolar bone resorption, and promotion of bone regeneration, which is superior to the treatment of a commercial gel. These findings suggest that MH/GRW gel with superiority in regulating bone homeostasis provides a promising therapeutic strategy for periodontitis.

Background: Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota's composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy's efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment., Methods: Subgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes., Results: We identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14-1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00-1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes., Conclusions: The shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles. Video Abstract., (© 2024. The Author(s).)

Abstrct: BACKGROUND: Apoptotic vesicles (ApoVs), which are extracellular vesicles released by apoptotic cells, have been reported to exhibit substantial therapeutic potential for inflammatory diseases and tissue regeneration. While extensive research has been dedicated to mesenchymal stem cells (MSCs), the investigation into immune cell-derived ApoVs remains limited, particularly regarding the function and fate of macrophage-derived ApoVs in the context of periodontitis (PD)., Results: Our study corroborates the occurrence and contribution of resident macrophage apoptosis in Porphyromonas gingivalis (Pg)-associated PD. The findings unveil the pivotal role played by apoptotic macrophages and their derived ApoVs in orchestrating periodontal bone remodeling. The enrichments of diverse functional miRNAs within these ApoVs are discerned through sequencing techniques. Moreover, our study elucidates that the macrophage-derived ApoVs predominantly deliver miR-143-3p, targeting insulin-like growth factor-binding protein 5 (IGFBP5), thereby disrupting periodontal bone homeostasis., Conclusions: Our study reveals that macrophages in Pg-associated PD undergo apoptosis and generate miR-143-3p-enriched ApoVs to silence IGFBP5, resulting in the perturbation of osteogenic-osteoclastic balance and the ensuing periodontal bone destruction. Accordingly, interventions targeting miR-143-3p in macrophages or employment of apoptosis inhibitor Z-VAD hold promise as effective therapeutic strategies for the management of PD., (© 2024. The Author(s).)

This study quantified the production of the pro-resolving agent Resolvin E1 by peripheral blood mononuclear cells (PBMC) from 20 systemically healthy volunteers with and without periodontitis after stimulation with lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg). Ten periodontitis patients and 10 healthy volunteers (30-50 years old), matched by age and sex, were recruited. Peripheral blood mononuclear cells were isolated and stimulated in culture plates for 24 hours with Pg LPS. Resolvin E1 levels were measured in the supernatants by enzyme-linked immunosorbent assay. Significantly higher production of Resolvin E1 was observed in both groups when stimulated with LPS compared to baseline levels (p<0.001). A significant increase in Resolvin E1 was observed in the presence of Lipopolysaccharide in the patients with periodontitis compared to the healthy group (p=0.0019). Resolvin E1 levels may reflect a measure of resolution of inflammation that warrants further clinical investigation.

Purpose: This study evaluated the therapeutic efficacy of combining Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) laser with subgingival curettage and root planing (SRP) in generalised stage III/grade C periodontitis patients and its effects on cytokine dynamics and microbial community., Materials and Methods: Fifteen patients diagnosed with stage III/grade C periodontitis were included in the cohort. The right and left sides of the mouth were randomly assigned either the conventional SRP (control) group or the SRP supplemented with Nd:YAG laser group (experimental group, 160 mJ, 4 W) in a split-mouth design. Clinical periodontal indices were recorded at baseline and at the 6-week follow-up post-treatment. ELISA was utilised to measure IL-1β and TNF-α levels in gingival crevicular fluid. The subgingival microbiota's composition and variations were characterised using 16S rDNA amplicon sequencing, while quantitative real-time polymerase chain reaction (qRT-PCR) was employed to analyse the changes in the red-complex bacteria in subgingival plaque., Results: The SRP&#43;Nd group exhibited a statistically significant reduction in record probing depth (PD) and bleeding on probing (BOP) compared to the SRP group after treatment (p0.05). The SRP&#43;Nd group showed a markedly lower IL-1β level than the SRP group (p0.05). Furthermore, there was no statistically significant difference in the dominant subgingival microbiota composition and level of the red-complex bacteria between the two groups (p>0.05)., Conclusion: The adjunctive use of Nd:YAG laser with SRP demonstrates promising short-term therapeutic benefits for patients with extensive stage III/grade C periodontitis. Both SRP as a standalone treatment and its combination with Nd:YAG laser effectively facilitate a transition in the dominant bacterial community from periodontitis-associated to periodontal health-associated microbiota.

Periodontitis exacerbates Alzheimer's disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APP swe /PS1 ΔE9 (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD., (© 2024. The Author(s).)

Dental infections, such as apical Periodontitis, periodontitis, and peri-implantitis (PI), are closely associated with specific bacterial species, including Streptococcus mutans (S. mutans), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum), among others. Antibiotics are extensively utilized for prophylactic and therapeutic purposes in the treatment of dental infections and other dental-related issues. Unfortunately, the rapid emergence of antimicrobial resistance has accompanied the increased use of antibiotics in recent years. Specific bacterial pathogens have reached a critical stage of antibiotic resistance, characterized by the proliferation of pan-resistant strains and the scarcity of viable therapeutic alternatives. Therapeutic use of particular bacteriophage (phage) particles that target bacterial pathogens is one potential alternative to antibiotics that are now being seriously considered for treating bacterial illnesses. A kind of virus known as a phage is capable of infecting and eliminating bacteria. Because they can't infect cells in plants and animals, phages might be a harmless substitute for antibiotics. To control oral disorders including periodontitis and dental caries, several research have been conducted in this area to study and identify phages from human saliva and dental plaque. The capacity of these agents to disturb biofilms expands their effectiveness against dental plaque biofilms and oral pathogens in cases of periodontitis, PI, and apical periodontitis. This review summarizes the current antibacterial properties of phages used to treat a variety of dental infections, such as periodontitis, peri-implantitis, infected dentin, and apical periodontitis., (© 2024. The Author(s).)

Oral pathobionts are essential in instigating local inflammation within the oral cavity and contribute to the pathogenesis of diseases in the gastrointestinal tract and other distant organs. Among the Gram-negative pathobionts, Porphyromonas gingivalis and Fusobacterium nucleatum emerge as critical drivers of periodontitis, exerting their influence not only locally but also as inducers of gut dysbiosis, intestinal disturbances, and systemic ailments. This dual impact is facilitated by their ectopic colonization of the intestinal mucosa and the subsequent mediation of distal systemic effects by releasing outer membrane vesicles (OMVs) into circulation. This review elucidates the principal components of oral pathobiont-derived OMVs implicated in disease pathogenesis within the oral-gut axis, detailing virulence factors that OMVs carry and their interactions with host epithelial and immune cells, both in vitro and in vivo. Additionally, we shed light on the less acknowledged interplay between oral pathobionts and the gut commensal Akkermansia muciniphila , which can directly impede oral pathobionts' growth and modulate bacterial gene expression. Notably, OMVs derived from A. muciniphila emerge as promoters of anti-inflammatory effects within the gastrointestinal and distant tissues. Consequently, we explore the potential of A. muciniphila -derived OMVs to interact with oral pathobionts and prevent disease in the oral-gut axis.

Background: Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection., Results: The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis-induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice., Conclusions: High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients., (© 2024. The Author(s).)

Background: Monkeys are an appropriate model for periodontal research owing to their similar dental anatomy and physiology unlike humans. Extensive literature exists on pathological periodontitis in monkeys and humans, although concerns regarding whether healthy middle-aged monkeys and humans display the same periodontal and oral microbial status remains unclear., Aims and Objectives: The current study aimed to compare alveolar bone resorption, gingival inflammatory infiltrate, and salivary microbiota profile in periodontally healthy middle-aged humans and monkeys., Methods: CBCT examination and histological analysis were performed to compare the periodontal status in middle-aged healthy humans and monkeys. Oral saliva16S rRNA sequencing was performed to analyze the oral microbial profile., Results: The alveolar resorption was compared between humans and monkeys, to determine the periodontal health. The percentage attachment of attachment loss was more around the posteriors teeth in humans when compared to monkeys (p<0.05). The degree of gingival inflammation was analyzed in both the groups, the expression of CD 34,45was higher in humans. 16S rRNA analysis demonstrated less diversity of salivary microorganisms in humans than in monkeys. The relative abundance of Aggregatibacter, Haemophilus, Gemella, and Porphyromonas at the genus level was significantly less in humans than in monkeys (p(<0.05)., Conclusion: The periodontally healthy middle-aged humans and monkeys display different alveolar bone resorption and gingival inflammatory infiltrate levels. Furthermore, the salivary microbiota profile showed distinctly different oral microbiomes in these two primates. Our results suggest that the difference in alveolar bone status and gingival inflammatory infiltrate in healthy humans and monkeys might be associated with the diversity of the oral microbiome., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Lin 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.)

This systematic review and network meta-analysis aimed to assess the impact of combining professional mechanical plaque removal (PMPR) with probiotics compared to PMPR + placebo on probing pocket depth (PPD) and clinical attachment level (CAL). Randomized controlled trials published until November 2023 were searched across electronic databases, peer-reviewed journals, and grey literature. Two authors independently selected, extracted data, and assessed bias risk. Primary outcomes were mean changes in PPD and CAL. Secondary outcomes included mean changes in bleeding on probing (BOP), plaque index, and colony-forming units. Network meta-analysis with the frequentist weighted least squares approach evaluated the data quantitatively, and CINeMA framework evaluated the quality of evidence. In 33 articles involving 1290 patients, results were stratified by follow-up period (short and long-time studies) and sensitivity analyses conducted based on probiotic therapy duration (1 month reference). Network meta-analysis revealed significant mean differences in PPD for nine probiotic interventions, CAL for eighteen interventions, and BOP for eight interventions, with Lactobacillus demonstrating the most substantial effects. Combining PMPR with probiotics as adjuvants to subgingival instrumentation may be more effective in improving PPD and CAL. Lactobacillus emerged as the most comprehensive and effective among the studied probiotic., (© 2024. The Author(s).)

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, which leads to neuroinflammation. The bacteria destroy periodontal tissue through virulence factors, which are retained in the bacteria's outer membrane vesicles (OMV). This study aimed to determine the real-time effect of an intraperitoneal injection of P. gingivalis OMV on the production and expression of inflammatory markers and histopathological changes in adult zebrafishes' central nervous systems (CNS). Following the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMVs, and the control group were injected with normal saline at seven different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA, and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 min, while IL-1β and IL-6 were expressed at subsequent 12 h and 24 h time points, respectively. Histopathological changes such as blood coagulation, astrocytosis, edema, spongiosis, and necrosis were observed between the 6hour and 24 h time points. The two apoptotic enzymes, caspases 3 and 9, were not expressed at any point. In summary, the OMV-induced neuroinflammatory responses and histopathological changes in adult zebrafish were time-point dependent. This study will enrich our understanding of the mechanism of P. gingivalis OMVs in neuroinflammation in a zebrafish model, most especially the timing of the expression of inflammatory mediators in relation to observable changes in brain tissues.

Periodontitis presents significant treatment challenges due to its complexity and potential complications. In response, an in situ forming gel (ISG) loaded with moxifloxacin HCl (Mx) and cellulose acetate butyrate (CAB) was developed for targeted periodontitis therapy. Mx-loaded 10-45% CAB-based ISGs were developed, and their physicochemical properties such as rheology, viscosity, contact angle, gel morphology and gel formation, interface interaction were investigated. Moreover, the formulation performance studies including drug release and kinetics, in vitro degradation, and antimicrobial activities were also evaluated. The Mx-loaded ISGs containing 25-45% CAB demonstrated rapid matrix formation in both macroscopic and microscopic examinations and presented plastic deformation matrix. Tracking with sodium fluorescein and Nile red fluorescence probes indicated delayed solvent movement owing to CAB matrix formation. Adequate CAB content sustained Mx release for one week, following Peppas-Sahlin model and indicating a predominantly Fickian diffusion mechanism. Higher CAB content likely contributed to a denser matrix structure, leading to a slower in vitro degradation rate. Synchrotron radiation X-ray tomographic and SEM imaging provided insights into the CAB matrix structure and porous network formation. These ISG formulations effectively inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, and Porphyromonas gingivalis. The Mx-loaded 40% CAB-based ISG shows promise as a dosage form for treating periodontitis. Further clinical trials are necessary to ensure the safety of this new ISG formulation, despite existing safety data for other medicinal uses of CAB. HIGHLIGHTS: Moxifloxacin HCl-loaded 10-45% cellulose acetate butyrate (CAB)-based in situ forming gels (ISG) were developed. They were evaluated for physicochemical properties, drug release, in vitro degradation, and antimicrobial activities. ISGs with 25-45% CAB showed swift matrix formation and plastic deformation Adequate CAB content sustained Mx release with Fickian diffusion mechanism They promise for periodontitis treatment because of effective inhibition of related pathogens., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

To better understand the link between periodontitis and metabolic diseases, our in vitro study aimed to assess the influence of the adipokine apelin and/or the periodontal pathogen Fusobacterium nucleatum on periodontal cells. Periodontal ligament (PDL) cells were exposed to F. nucleatum in the presence and absence of apelin. Scratch assays were used to analyze the in vitro wound healing and velocity of cell migration. To investigate if F. nucleatum and/or apelin have a regulatory effect on cell proliferation and apoptosis, proliferation and viability assays were performed as well as an analysis of caspase 9 expression. Both the in vitro wound closure and the cell migration rate were significantly reduced by F. nucleatum. Simultaneous incubation with apelin counteracted the adverse effects of F. nucleatum . The proliferation assay demonstrated that neither apelin nor F. nucleatum significantly affected PDL cell proliferation. Furthermore, neither apelin nor F. nucleatum was cytotoxic or affected apoptosis after 48 h. Apelin could play a modulatory role in the pathogenesis of periodontitis, as it was able to compensate for the inhibitory effects of the periodontal pathogen F. nucleatum on PDL cell migration in vitro.

The role of the oral microbiome in mental health has recently been appreciated within the proposed oral-brain axis. This study examined the structure and composition of the salivary microbiome in a large-scale population-based cohort of individuals reporting mental health symptoms (n = 306) compared to mentally healthy controls (n = 164) using 16S rRNA sequencing. Mental health symptoms were evaluated using validated questionnaires and included depression, anxiety, and posttraumatic stress disorder (PTSD), with accompanying periodontal outcomes. Participants also indicated current or previous diagnoses of anxiety, depression, periodontitis, and gingivitis. Mental and periodontal health variables influenced the overall composition of the oral microbiome. PTSD symptoms correlated with a lower clr-transformed relative abundance of Haemophilus sputorum and a higher clr-transformed relative abundance of Prevotella histicola. The clr-transformed relative abundance of P. histicola was also positively associated with depressive scores and negatively associated with psychological quality of life. Anxiety disorder diagnosis was associated with a lower clr-transformed relative abundance of Neisseria elongate and a higher clr-transformed relative abundance of Oribacterium asaccharolyticum. A higher clr-transformed relative abundance of Shuttleworthia and lower clr-transformed relative abundance of Capnocytophaga were evident in those who reported a clinical periodontitis diagnosis. Higher Eggerthia and lower Haemophilus parainfluenzae clr-transformed relative abundances were associated with reported clinical periodontitis diagnoses and psychotherapeutic efficacy. Functional prediction analysis revealed a potential role for tryptophan metabolism/degradation in the oral-brain axis, which was confirmed by lower plasma serotonin levels across symptomatic groups. This study sheds light on the intricate interplay between oral microbiota, periodontal and mental health outcomes, and a potential role for tryptophan metabolism in the proposed oral-brain axis, emphasizing the need for further exploration to pave the way for novel therapeutic interventions and predicting therapeutic response., (© 2024. The Author(s).)

Background: Plaque biofilm is a major etiologic factor of periodontitis, and its effective removal prevents or ameliorates the disease. However, toothbrushing alone does not sufficiently clean the interdental area, and additional interdental cleaning is required to completely remove the plaque from this locale. This cross-sectional study aimed to assess the association of interdental cleaning on the prevalence of periodontitis in a large urban Thai adult cohort., Methods: Interdental cleaning data were retrieved from a dental survey of 1,743 employees of the Electricity Generating Authority of Thailand (EGAT) in 2019. The Centers for Disease Control and Prevention/American Association of Periodontology (CDC/AAP) periodontal case definitions were applied. The participants were subdivided into two groups as those with or without periodontitis depending on their oral health status assessed by calibrated professional examiners. The proportion of subjects who performed interdental cleaning was assessed through a self-reported questionnaire by frequency (daily/ ≥ 1 per week/ none) and profile (correct/ incorrect) of interdental cleaning. Then, the association between interdental cleaning and periodontitis was calculated using logistic regression analysis controlling for the common risk factors of periodontitis such as age, sex, education, smoking, and diabetes., Results: Participants who performed interdental cleaning on a daily basis and ≥ 1 per week were 27.5% (95% CI: 25.4, 29.6) and 29.1% (95% CI: 27.0, 31.3), respectively while the remainder did not practice. Of those who used interdental cleaning, about one-half focused on sites with food impaction. There was a significant 44% lower prevalence of periodontitis (adjusted odds ratio of 0.56 (95%CI: 0.40, 0.79) in the cohort with a frequent and correct group., Conclusions: Our data indicate an inverse association between interdental cleaning and periodontitis, particularly in those who routinely adhered to it. Regular interdental cleaning is likely to have a salutary effect on oral health., Trial Registration: The study was registered retrospectively in Thai Clinical Trials Registry, Registration number: TCTR20240817005, on 17 Aug 2024 ( https://www.thaiclinicaltrials.org )., (© 2024. The Author(s).)

Antiseptics are widely used in oral healthcare to prevent or treat oral diseases, such as gingivitis and periodontitis. However, the incidence of bacteria being tolerant to standard antiseptics has sharply increased over the last few years. This stresses the urgency for surveillance against tolerant organisms, as well as the discovery of novel antimicrobials. Traditionally, susceptibility to antimicrobials is assessed by broth micro-dilution or disk diffusion assays, both of which are time-consuming, labor-intensive, and provide limited information on the mode of action of the antimicrobials. The abovementioned limitations highlight the need for the development of new methods to monitor and further understand antimicrobial susceptibility. In this study, we used real-time flow cytometry, combined with membrane permeability staining, as a quick and sensitive technology to study the quantitative and qualitative responses of two oral pathobionts to different concentrations of chlorhexidine (CHX), cetylpyridinium chloride (CPC), or triclosan. Apart from the real-time monitoring of cell damage, we further applied a phenotypic fingerprinting method to differentiate between the bacterial subpopulations that arose due to treatment. We quantified the pathobiont damage rate of different antiseptics at different concentrations within 15 minutes of exposure and identified the conditions under which the bacteria were most susceptible. Moreover, we detected species-specific and treatment-specific phenotypic subpopulations. This proves that real-time flow cytometry can provide information on the susceptibility of different microorganisms in a short time frame while differentiating between antiseptics and thus could be a valuable tool in the discovery of novel antimicrobial compound, while at the same time deciphering their mode of action., Importance: With increasing evidence that microorganisms are becoming more tolerant to standard antimicrobials, faster and more accessible antimicrobial susceptibility testing methods are needed. However, traditional susceptibility assays are laborious and time-consuming. To overcome the abovementioned limitations, we introduce a novel approach to define antimicrobial susceptibility in a much shorter time frame with the use of real-time flow cytometry. Furthermore, phenotypic fingerprinting analysis can be applied on the data to study the way antiseptics affect the bacterial cell morphology over time and, thus, gain information on the mode of action of a certain compound., Competing Interests: The authors declare no conflict of interest.

Introduction. Negative changes in the microbial composition have been extensively studied in individuals with periodontal disease. Gap Statement. The changes in the oral microbiota after treating this disease are still unknown. Aim. We sought to elucidate the distinctive traits of salivary microbiota in individuals displaying healthy gums and those with severe periodontitis (SP) and examine the influence of periodontal therapy. Methodology. Periodontal pocket depths were examined to determine disease severity. The presence and quantity of oral Helicobacter pylori (associated with periodontal disease) were determined. Sequencing of 16S ribosomal DNA and bioinformatic analyses were performed to assess oral bacterial compositions in patients. Results. Sequencing analysis of 16S ribosomal DNA revealed a significant reduction in the abundance of operational taxonomic units (OTUs) and Chao1 and Abundance coverage-based estimator(ACE) indices in the oral cavities of individuals with SP compared to those of the healthy controls. However, these parameters showed significant recovery after appropriate treatment severe periodontitis after treatment (TSP). Additionally, the levels of harmful Bacillales and Spirochetes significantly increased, whereas the presence of beneficial Euryarchaeota significantly decreased in the SP group. The TSP group exhibited considerably augmented abundances of Burkholderiaceae and Veillonella, while noteworthy reductions in the pathogenic microbiota (Clostridia, Fusobacteria and Spirochaetes) were noticed compared to those of the SP group. Functionally, these modified OTUs were extensively implicated in 41 metabolic pathways. Conclusion. Our study demonstrates that nonsurgical periodontal therapy can effectively reduce the diversity of the oral microbiota, thereby potentially enhancing the treatment efficacy in patients with periodontal disease.

Background. Bacteria significantly influence human health and disease, with bacterial biosynthetic gene clusters (BGCs) being crucial in the microbiome-host and microbe-microbe interactions. Gap statement. Despite extensive research into BGCs within the human gut microbiome, their roles in the oral microbiome are less understood. Aim. This pilot study utilizes high-throughput shotgun metagenomic sequencing to examine the oral microbiota in different niches, particularly focusing on the association of BGCs with periodontitis. Methodology. We analysed saliva, subgingival plaque and supragingival plaque samples from periodontitis patients ( n =23) and controls ( n =16). DNA was extracted from these samples using standardized protocols. The high-throughput shotgun metagenomic sequencing was then performed to obtain comprehensive genetic information from the microbial communities present in the samples. Results. Our study identified 10 742 BGCs, with certain clusters being niche-specific. Notably, aryl polyenes and bacteriocins were the most prevalent BGCs identified. We discovered several 'novel' BGCs that are widely represented across various bacterial phyla and identified BGCs that had different distributions between periodontitis and control subjects. Our systematic approach unveiled the previously unexplored biosynthetic pathways that may be key players in periodontitis. Conclusions. Our research expands the current metagenomic knowledge of the oral microbiota in both healthy and periodontally diseased states. These findings highlight the presence of novel biosynthetic pathways in the oral cavity and suggest a complex network of host-microbe and microbe-microbe interactions, potentially influencing periodontal disease. The BGCs identified in this study pave the way for future investigations into the role of small-molecule-mediated interactions within the human oral microbiota and their impact on periodontitis.

Background: Malondialdehyde-acetaldehyde (MAA) adducts lead to generation of anti-MAA autoantibodies and have been independently identified in inflamed periodontal and rheumatoid arthritis (RA) tissues. This study evaluates serum samples from RA cases and osteoarthritis (OA) controls to quantify associations between periodontal clinical measures, alveolar bone loss (ABL), and anti-Porphyromonas gingivalis, anti-Prevotella intermedia, and anti-Fusobacterium nucleatum antibody concentrations with anti-MAA antibody concentrations., Methods: Participants (n = 284 RA cases, n = 330 OA controls) underwent periodontal clinical assessments and ABL measurements. Serum immunoglobulin (Ig) A, IgG, and IgM anti-MAA and serum IgG antibacterial antibody concentrations were quantified by enzyme-linked immunosorbent assay (ELISA). Analyses utilized simple linear regression and multivariable adjusted models., Results: No significant associations of periodontal clinical measures with serum anti-MAA were found. Moderate (p = 0.038 and p = 0.036, respectively) and high ABL (p = 0.012 and p = 0.014, respectively) in RA cases (but not in OA) were positively associated with IgG and IgM anti-MAA. Anti-P. gingivalis and anti-P. intermedia antibody concentrations were positively associated with IgA (p = 0.001 for both), IgG (p = 0.007 and p = 0.034, respectively), and IgM anti-MAA antibody concentrations (p < 0.001 and p = 0.020, respectively), while anti-F. nucleatum was positively associated with IgG anti-MAA (p = 0.042), findings that were similar across groups., Conclusions: A positive association was demonstrated between ABL and serum IgG and IgM anti-MAA antibody concentrations that was unique to RA and not observed in OA. Serum anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations displayed significant associations with anti-MAA antibody in both groups. These findings suggest MAA may play a role in the interrelationship between the periodontium and RA., (© 2024 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Introduction: The worldwide prevalence of periodontitis is considerably high, and its pathogenic mechanisms must be investigated and understood in order to improve clinical treatment outcomes and reduce the disease prevalence and burden. The exacerbation of the host immune system induced by oral microbial dysbiosis and the subsequent tissue destruction are the hallmarks of the periodontitis. However, the oral bacteria involved in periodontitis are not fully understood. We used the Oxford Nanopore Technologies (ONT) sequencing system to analyze metagenomic information in subgingival dental plaque from periodontitis and non-periodontitis patients. The number of Lactobacillus zeae (L. zeae) in the periodontitis patients was 17.55-fold higher than in the non-periodontitis patients, suggesting that L. zeae is a novel periodontitis-associated pathogen. Although several Lactobacillus species are used in vivo as probiotics to treat periodontitis and compete with Porphyromonas gingivalis (P. gingivalis), the roles of L. zeae in periodontitis progression, and the relationship between L. zeae and P. gingivalis needs to be investigated., Methods: Both L. zeae and P. gingivalis were inoculated in the ligature-implant site of periodontitis mice. We collected mouse gingival crevicular fluid to analyze inflammatory cytokine secretion using a multiplex assay. Intact or sliced mouse maxilla tissue was used for micro-computed tomography analysis or hematoxylin and eosin staining, immunohistochemistry, and tartrate-resistant acid phosphatase staining to evaluate alveolar bone loss, neutrophil infiltration, and osteoclast activation, respectively., Results: We observed that L. zeae competed with P. gingivalis, and it increased inflammatory cytokine secretion at the ligature-implant site. Similar to P. gingivalis, L. zeae promoted ligature-induced neutrophile infiltration, osteoclast activation, and alveolar bone loss., Discussion: We, therefore, concluded that L. zeae accelerated the progression of periodontitis in the ligature-induced periodontitis mouse model., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pathobionts associated with periodontitis, such as Treponema denticola, must possess numerous sensory transduction systems to adapt to the highly dynamic subgingival environment. To date, the signaling pathways utilized by T. denticola to rapidly sense and respond to environmental stimuli are mainly unknown. Bis-(3'-5') cyclic diadenosine monophosphate (c-di-AMP) is a nucleotide secondary messenger that regulates osmolyte transport, central metabolism, biofilm development, and pathogenicity in many bacteria but is uncharacterized in T. denticola. Here, we studied c-di-AMP signaling in T. denticola to understand how it contributes to T. denticola physiology. We demonstrated that T. denticola produces c-di-AMP and identified enzymes that function in the synthesis (TDE1909) and hydrolysis (TDE0027) of c-di-AMP. To investigate how c-di-AMP may impact T. denticola cellular processes, a screening assay was performed to identify putative c-di-AMP receptor proteins. This approach identified TDE0087, annotated as a potassium uptake protein, as the first T. denticola c-di-AMP binding protein. As potassium homeostasis is critical for maintaining turgor pressure, we demonstrated that T. denticola c-di-AMP concentrations are impacted by osmolarity, suggesting that c-di-AMP negatively regulates potassium uptake in hypoosmotic solutions. Collectively, this study demonstrates T. denticola utilizes c-di-AMP signaling, identifies c-di-AMP metabolism proteins, identifies putative receptor proteins, and correlates c-di-AMP signaling to osmoregulation., (© 2024 The Authors. Molecular Oral Microbiology published by John Wiley & Sons Ltd.)

Peri-implantitis (PI) is a chronic, inflammatory, and infectious disease which affects dental implants and has certain similarities to periodontitis (PD). Evidence has shown that PD may be related to several types of systemic disorders, such as diabetes and insulin resistance, cardiovascular diseases, respiratory tract infections, adverse pregnancy outcomes, and neurological disorders. Furthermore, some types of bacteria in PD can also be found in PI, leading to certain similarities in the immunoinflammatory responses in the host. This review aims to discuss the possible connection between PI and neuroinflammation, using information based on studies about periodontal disorders, a topic whose connection with systemic alterations has been gaining the interest of the scientific community. Literature concerning PI, PD, and systemic disorders, such as neuroinflammation, brain inflammation, and neurological disorder, was searched in the PubMed database using different keyword combinations. All studies found were included in this narrative review. No filters were used. Eligible studies were analyzed and reviewed carefully. This study found similarities between PI and PD development, maintenance, and in the bacterial agents located around the teeth (periodontitis) or dental implants (peri-implantitis). Through the cardiovascular system, these pathologies may also affect blood-brain barrier permeability. Furthermore, scientific evidence has suggested that microorganisms from PI (as in PD) can be recognized by trigeminal fiber endings and start inflammatory responses into the trigeminal ganglion. In addition, bacteria can traverse from the mouth to the brain through the lymphatic system. Consequently, the immune system increases inflammatory mediators in the brain, affecting the homeostasis of the nervous tissue and vice-versa. Based on the interrelation of microbiological, inflammatory, and immunological findings between PD and PI, it is possible to infer that immunoinflammatory changes observed in PD can imply systemic changes in PI. This, as discussed, could lead to the development or intensification of neuroinflammatory changes, contributing to neurodegenerative diseases., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Objective: This observational study aimed to explore the metagenomics of subgingival biofilms in individuals with varying degrees of asthma, from severe to none, to elucidate the association between the subgingival microbiome and asthma., Materials and Methods: Subgingival biofilm samples were collected from thirty participants at the Asthma Control Program Outpatient Clinic in Bahia (ProAR). These samples were categorized into six groups based on the severity of asthma and the presence or absence of periodontitis. We employed next-generation sequencing (Illumina MiSeq), targeting the 16S rRNA gene, to characterize the microbial communities present. Our analysis included descriptive statistics and sequencing data, evaluated using multivariate statistical methods such as the Shannon index, principal coordinate analysis, and the Bray-Curtis dissimilarity., Results: Our findings indicate a higher prevalence of periodontally detrimental bacterial genera in individuals with severe asthma and periodontitis. Additionally, individuals with asthma, but without periodontitis, exhibited a tendency toward dysbiosis, particularly in cases of severe asthma., Conclusion: This research provides new insights into the composition of the subgingival microbiome in individuals with varying severities of asthma and periodontitis. The genera identified in this study underscore the need for further investigations to build upon these findings., (© 2024 Wiley Periodicals LLC.)

Aim: Periodontitis is a potential risk factor for preterm birth (PTB) in women; however, the causal relationship or the exact mechanism remain unknown. This study aimed to compare the oral microbiome features of mothers with full-term birth (FTB) with those who had preterm delivery., Methods: This study prospectively enrolled 60 women (30 mothers with PTB and 30 mothers with FTB), and subgingival plaque samples were collected and analysed by metagenomic 16S rDNA sequencing. Clinical measurements, including periodontal probing depth, clinical attachment level, modified gingival index (mGI) and plaque index, were performed to determine the periodontal state of the participants. Medical and obstetric data were collected as well., Results: Among the periodontal measurements, mGI score, reflecting the level of gingival inflammation, exhibited a statistically significant association with PTB (adjusted odds ratio 2.705, 95% confidence interval 1.074-6.811, p = .035). When subgroup analysis was conducted based on mean mGI scores (mGI ≥ 2, high inflammation [HI] versus mGI < 2, low inflammation [LI]), microbiome analysis revealed clear distinctions in microbial compositions between PTB and FTB mothers in both the HI and LI groups. Especially in the HI group, alpha diversity exhibited a decreasing trend in PTB mothers compared to FTB mothers. Beta diversity also revealed significant differences between the two groups. In Linear Discriminant Analysis Effect Size analysis, certain anaerobic taxa, including the genera Spirochaetes, Treponema and Porphyromonas, were relatively abundant in the FTB/HI group, whereas the PTB/HI group showed a high abundance of the order Actinomycetales. Network analysis showed that the FTB/HI had relatively stronger connectivity in microbial composition than the PTB/HI group. Dysbiosis ratio of plaque microbiome, in terms of periodontitis, was significantly lower in PTB/HI group compared to FTB/HI group., Conclusion: The compositions of maternal subgingival microbiomes differed between PTB and FTB mothers in both the high and low levels of gingival inflammation groups. In the presence of high level of gingival inflammation, dysbiosis in plaque microbiome, in terms of periodontitis, was decreased in PTB mothers compared to FTB mothers., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objective: Investigate the link between live dietary microbe consumption and the prevalence of periodontitis., Methods and Materials: National health and nutrition examination survey (2009-2014) data was used to assess the association among adults. Live dietary microbe intake was categorized as low or medium to high. Regression models were employed to assess this association, adjusting for demographic variables and other covariates. Examined dose-response relationship and conducted subgroup analyses by ethnicity, age and gender. Multiplicative interactions were evaluated using likelihood ratio tests., Results: The analysis included 8574 participants. After adjusting for various factors including age, gender, ethnicity, dietary habits, dietary inflammatory index, alcohol consumption, smoking status, hypertension, diabetes mellitus and oral health behaviors, individuals with daily intake of medium to high levels of live dietary microbes showed a significantly reduced risk of periodontitis compared to those who did not consume such microbes with a dose-response trend (p for trend <0.0001, p < 0.01). Significant differences in the impact of live microbe intake on periodontitis were also observed across different age groups in all Models (p for interaction ≤0.05)., Conclusion: Medium to high live dietary microbe consumption independently correlates with lower periodontitis risk, irrespective of traditional risk factors and demographics., (© 2024 Wiley Periodicals LLC.)

Periodontitis is a common oral bacterial infection characterized by inflammatory responses. Its high prevalence lowers the quality of life for individuals and increases the global economic and disease burden. As microorganisms in dental plaque are responsible for this oral disease, antibacterial drug treatments are effective strategies for preventing and treating periodontitis. In this study, we investigated the inhibitory effect of nicotinamide (NAM), a vitamin B 3 derivative, on the growth and virulence of Porphyromonas gingivalis, a key member of the red complex. Our findings revealed that NAM inhibited bacterial growth and gingipain activities, which played a dominant role in protein hydrolysis and heme acquisition. NAM decreased hemagglutination and hemolysis abilities and changed hemin and hemoglobin binding capacities, controlling bacterial infection through a starvation strategy by blocking access to growth-essential nutrients from the outside and reducing bacterial virulence. Several experiments in an animal model showed the effectiveness of NAM in preventing alveolar bone loss and reducing inflammatory cell infiltration, shedding light on its potential therapeutic applicability., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Immune cells residing at the gingiva experience diverse and unique signals, tailoring their functions to enable them to appropriately respond to immunological challenges and maintain tissue integrity. The gingiva, defined as the mucosal barrier that surrounds and supports the teeth, is the only barrier site completely transected by a hard structure, the tooth. The tissue is damaged in early life during tooth eruption and chronically throughout life by the process of mastication. This occurs alongside challenges typical of barrier sites, including exposure to invading pathogens, the local commensal microbial community and environmental antigens. This review will focus on the immune network safeguarding gingival integrity, which is far less understood than that resident at other barrier sites. A detailed understanding of the gingiva-resident immune network is vital as it is the site of the inflammatory disease periodontitis, the most common chronic inflammatory condition in humans which has well-known detrimental systemic effects. Furthering our understanding of how the immune populations within the gingiva develop, are tailored in health, and how this is dysregulated in disease would further the development of effective therapies for periodontitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) offers a promising antimicrobial strategy for periodontitis, yet faces challenges like complex material structure and limited NIR-I light penetration. Additionally, low endogenous H 2 O 2 levels in biofilm and a focus on bacterial eradication over colonization prevention limit current treatments. To address these issues, we newly introduce a single-material system (Cu 3 P@PAH@Lox) that integrates dual functionalities to synergistically enhance antimicrobial effects and significantly reduce pathogen co-aggregation. This system utilizes PTT to increase local temperature, boosting •OH production in CDT while downregulating heat shock proteins to enhance PTT efficacy, forming a self-reinforcing feedback loop. Lactate oxidase (Lox) is employed to convert lactate-a metabolite in periodontal biofilm-into H 2 O 2 , further amplifying CDT's potential. In vitro Cu 3 P@PAH@Lox demonstrates a remarkable synergistic effect against dual-species biofilms by more than 2-log reduction of colony-forming unit. Moreover, Cu 3 P@PAH@Lox exhibits outstanding synergistic antibacterial performances to alleviate inflammation and destruction of tissue in vivo periodontitis model. Furthermore, the mechanism of pathogen co-aggregation disruption by PTT is verified via the Cbe-Ltp1-Ptk1-fimA signaling pathway. This single-material multimodal system we have herein demonstrated for the first time marks a significant advancement in periodontitis treatment, eradicating microbes and preventing bacterial colonization, offering a path to comprehensive periodontal care. STATEMENT OF SIGNIFICANCE: The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising therapy for periodontitis. Yet, facing challenges, the complex material structure, limited NIR-I light penetration, low endogenous H 2 O 2 level in biofilm, and a focus on bacterial eradication over colonization prevention are still insufficient. This study pioneers a unique, single-material system (Cu 3 P@PAH@Lox) that synergistically enhances antimicrobial effects and substantially curtails pathogen co-aggregation, advancing periodontitis therapy. By exploiting PTT to elevate local temperatures, thereby increasing hydroxyl radical production in CDT and concurrently suppressing heat shock proteins, the system establishes a potent, self-enhancing loop. Furthermore, lactate oxidase is innovatively utilized to convert lactate from periodontal biofilm into hydrogen peroxide, augmenting the efficacy of CDT. The introduction of Cu 3 P@PAH@Lox is poised to revolutionize periodontitis treatment, eliminating microbes and impeding bacterial colonization, thereby charting a course for comprehensive periodontal management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Periodontitis is an inflammatory oral disease that occurs as a result of the damaging effects of the immune response against the subgingival microflora. Among the mechanisms involved, the nucleotide-binding oligomerization domain, leucine-rich repeat-containing proteins family member NLRP3 (NLR family pyrin domain-containing 3), proposed as the key regulator of macrophage-induced inflammation, is strongly associated with periodontal disease due to the bacterial activators. This paper aimed to present key general concepts of NLRP3 inflammasome activation and regulation in periodontal disease., Method: A narrative review was conducted in order to depict the current knowledge on the relationship between NLRP3 inflammasome activity and periodontal disease. In vitro and in situ studies were retrieved and commented based on their relevance in the field., Results: The NLRP3 inflammasome activity stimulated by periodontal microbiota drive periodontal disease pathogenesis and progression. This occurs through the release of proinflammatory cytokines IL-1β, IL-18, and DAMPs (damage-associated molecular pattern molecules) following inflammasome activation. Moreover, the tissue expression of NLRP3 is dysregulated by oral microbiota, further exacerbating periodontal inflammation., Conclusion: The review provides new insights into the relationship between the NLRP3 inflammasome activity and periodontal disease pathogenesis, highlighting the roles and regulatory mechanism of inflammatory molecules involved in the disease process., (© 2024 The Author(s). Oral Diseases published by Wiley Periodicals LLC.)

Porphyromonas gingivalis is a Gram-negative, anaerobic oral pathobiont, an etiological agent of periodontitis and the most commonly studied periodontal bacterium. Multiple low passage clinical isolates were sequenced, and their genomes compared to several laboratory strains. Phylogenetic distances were mapped, a gene absence-presence matrix generated, and core (present in all genomes) and accessory (absent in one or more genomes) genes delineated. Subsequently, a second pangenome delineating the prevalence of inherently essential genes was generated. The prevalence of genes conditionally essential for surviving tobacco exposure, abscess formation and epithelial invasion was also determined, in addition to genes encoding key proteolytic enzymes containing putative signal peptides. While the absolutely essential pangenome was highly conserved, significant differences in the complete and conditionally essential pangenomes were apparent. Thus, genetic plasticity appears to lie primarily in gene sets facilitating adaptation to variant disease-related environments. Those genes that are highly pervasive in the P. gingivalis absolutely essential pangenome or are highly prevalent and essential for fitness in disease-relevant models, may represent particularly attractive therapeutic targets worthy of further investigation. As mutations in absolutely essential genes are expected to be lethal, the data provided herein should also facilitate improved planning for P. gingivalis gene mutation strategies., (© 2024. The Author(s).)

Objectives: To investigate the supragingival microbiome surrounding dental implants and neighbouring tooth in periodontitis history and periodontally healthy patients., Methods: Subjects with a history of periodontitis (test) and periodontally healthy subjects (control) received one of two types of dental implants with different surface characteristics: sandblasted acid-etched (SLA) or precision dimension laser-treated (PDL). Periodontal clinical measurements were collected at baseline (V 1 ), 3 months after implant placement (V 4 ), at zirconia crown placement (V 6 ) and 3 months after zirconia crown placement (V 8 ). Supragingival bacterial microbiota was studied using Illumina MiSeq sequencing., Results: Supragingival microbial community on SLA implants in test group significantly differed to control group at V 8 (p < 0.05). A longitudinal shift displaying microbial dysbiosis occurred on SLA implants (p < 0.05) and adjacent teeth (p < 0.05) among test patients from V 6 to V 8 . On PDL implants and the adjacent tooth, no significant difference between test and control groups from V 6 to V 8 (p > 0.05). Co-occurrence network in test group of SLA implants and the adjacent tooth at V 8 showed increased disease-associated bacteria and reduced health-associated bacteria. Health-associated bacteria were dominant in control group of SLA implants at V 8 ., Conclusion: The surface characteristics and prosthetic components of dental implants may be important risk factors in patients with a history of periodontitis., Clinical Relevance: Dysbiosis of supragingival microbiome may predispose dental implants to peri-implant diseases. Thus, a strict supportive periodontal care plan is imperative to prevent early onset of biological complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aims to analyse the association between the baseline microbial load of selected periodontopathogenic bacteria collected from gingival crevicular fluid (GCF) and the primary outcome of steps I and II therapy., Materials and Methods: 222 patients with stage III periodontitis were included into this retrospective analysis that received steps 1 and 2 periodontal therapy without adjunctive systemic antibiotics. Baseline GCF samples were quantitatively analysed using ELISA-based kits for levels of periodontopathogens (Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Treponema denticola (Td), and Tannerella forsythia (Tf)) and associated with the primary therapy outcome using a "treat-to-target" therapy endpoint (TE) defined as ≤ 4 sites with PD ≥ 5 mm six months after therapy., Results: 38.2% of the patients achieved TE. Patients failing to achieve TE revealed significantly increased levels of Pg, Fn, and Tf at baseline (Pg: p = 0.010, Fn: p = 0.008 Tf: p = 0.004). Multivariate binary logistic regression adjusted for sex, mean probing depth, diabetes, and current smoking status showed an independent relationship between Tf and the TE (aOR 2.570, p = 0.023)., Conclusion: Increased microbial load is associated with decreased responsiveness to therapy. The findings suggest that specifically baseline Tf levels are associated with poorer treatment outcomes and might improve the accuracy of periodontal diagnosis., Clinical Relevance: The findings of this study support the concept of a critical biomass that is sufficient to induce and maintain an immune response within the periodontal pocket, which ultimately leads to irreversible tissue destruction. However, calculating this level in advance may serve as an early indicator for intervention., Key Finding: Baseline Tannerella forsythia levels are associated with poorer treatment outcome., (© 2024. The Author(s).)

Objectives: This study aimed to explore the causal link between the gut microbiota and periodontitis, and to delineate and quantify the intermediary role of immune cells, so as to provide new insights into the pathogenesis, prevention and treatment of periodontitis., Materials and Methods: We employed a two-sample Mendelian randomization (MR) approach to analyze the genetic predictors of gut microbiota composition (covering 412 gut microbiota taxa and functions) and periodontitis (involving 4,784 cases and 272,252 controls) derived from genome-wide association study (GWAS) datasets. A subsequent two-step MR analysis was conducted to evaluate the extent to which immune cell traits (encompassing 731 immune cell characteristics) mediate the influence of gut microbiota on periodontitis risk., Results: Our analysis implicated nine gut microbiota taxa as causal factors in periodontitis susceptibility (p < 0.05). Notably, the Genus Roseburia was identified as exerting a protective effect against periodontitis, partially mediated through the upregulation of CD86 expression on granulocytes, with an 8.15% mediation effect observed., Conclusions: Our findings establish a causal relationship between the gut microbiota and periodontitis, highlighting the protective role of Roseburia against this condition. A notable proportion of this protective effect is mediated via the upregulation of CD86 on granulocytes., Clinical Relevance: It can provide new ideas for the pathogenesis, prevention and treatment for periodontitis through exploring the causal link between the gut microbiota and periodontitis, and describing and quantifying the intermediary role of immune cells., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs)., Design: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related β-galactosidase (SA-β-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry., Results: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-β-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05)., Conclusions: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Periodontitis is a chronic inflammatory disease driven by dysbiosis in subgingival microbial communities leading to increased abundance of a limited number of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Oral health, particularly periodontitis, is a modifiable risk factor for Alzheimer disease (AD) pathogenesis, with components of both these bacteria identified in postmortem brains of persons with AD. Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers. P. gingivalis displays synergistic virulence with T. denticola during periodontitis. The aim of the current study was to determine the ability of P. gingivalis and T. denticola, grown in physiologically relevant conditions, individually and in combination, to induce AD-like pathology following chronic oral inoculation of female mice over 12 weeks. P. gingivalis alone significantly increased all 7 brain pathologies examined: neuronal damage, activation of astrocytes and microglia, expression of inflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 and production of amyloid-β plaques and hyperphosphorylated tau, in the hippocampus, cortex and midbrain, compared to control mice. T. denticola alone significantly increased neuronal damage, activation of astrocytes and microglia, and expression of IL-1β, in the hippocampus, cortex and midbrain, compared to control mice. Coinoculation of P. gingivalis with T. denticola significantly increased activation of astrocytes and microglia in the hippocampus, cortex and midbrain, and increased production of hyperphosphorylated tau and IL-1β in the hippocampus only. The host brain response elicited by oral coinoculation was less than that elicited by each bacterium, suggesting coinoculation was less pathogenic., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Periodontitis is a common chronic inflammatory disease, affecting approximately 19% of the global adult population. A relationship between periodontal disease and Alzheimer disease has long been recognized, and recent evidence has been uncovered to link these 2 diseases mechanistically. Periodontitis is caused by dysbiosis in the subgingival plaque microbiome, with a pronounced shift in the oral microbiota from one consisting primarily of Gram-positive aerobic bacteria to one predominated by Gram-negative anaerobes, such as Porphyromonas gingivalis. A common phenomenon shared by all bacteria is the release of membrane vesicles to facilitate biomolecule delivery across long distances. In particular, the vesicles released by P gingivalis and other oral pathogens have been found to transport bacterial components across the blood-brain barrier, initiating the physiologic changes involved in Alzheimer disease. In this review, we summarize recent data that support the relationship between vesicles secreted by periodontal pathogens to Alzheimer disease pathology., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sex is an often overlooked, yet compulsory, biological variable when performing biomedical research. Periodontitis is a common yet progressively debilitating chronic inflammatory disorder affecting the tissues supporting teeth that ultimately leads to tooth loss if left untreated. The incidence of periodontitis is sex biased, with increased prevalence in males compared with females but with unknown etiology. We performed a sex-specific meta-analysis using publicly available oral microbiome data from different sampling sites of patients with periodontitis and periodontally healthy controls; sex balance was established for each periodontal health condition. Our results show sex-based diversity in oral biofilms of individuals with periodontitis but not in their saliva, with increased abundance of several periodontal pathogens in subgingival plaques from females compared with males. We devised a quantitative measure, uniquely defined as the Microsexome Index (MSI), which indicates that sexual dimorphism in subgingival bacterial composition is a distinct feature of reduced microbial diversity during periodontitis but not under healthy conditions. In addition, we found that smoking exacerbates microsexome diversity in supragingival biofilms, particularly during periodontitis. Taken together, we provide insights regarding sex-based diversity in periodontitis, a disease with multiorgan associations, and provide the rationale for further mechanistic, diagnostic, and therapeutic studies.

Periodontitis is a chronic inflammatory disease that causes destruction of the periodontium and eventual tooth loss. The priority in the periodontal treatment is to remove the subgingival biofilm. Chemical removal of biofilms using antimicrobial agents has been applied in clinical practice. However, their clinical effect is still limited because the agents must overcome biofilm's significant drug tolerance, which is primarily caused by the extracellular matrix, a physical barrier that attenuates drug diffusion. This study aimed to study the use of ionic liquids (ILs), a new class of biocompatible materials, for controlling subgingival biofilms because of their excellent permeability. Choline and geranate (CAGE) IL was tested for its highly potent antiseptic behavior and permeability. Antibacterial tests revealed that the significant efficacy of CAGE against periodontopathic microorganisms was derived from their ability to destroy cell membrane, as demonstrated by membrane permeability assay and transmission electron microscopy imaging. Antibiofilm tests using two pathogenic biofilm models revealed that CAGE exerted efficacy against the biofilm-embedded bacteria, conspicuously neutralized the biofilms, and eventually destroyed the biofilm structure. Furthermore, the penetration of CAGE into the biofilm was visually confirmed using confocal laser scanning microscopy. This study highlighted the potential of CAGE as a powerful antibiofilm therapeutic., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Chunyang Yan reports equipment, drugs, or supplies was provided by FUTOKU foundation. Koichi Tabeta reports article publishing charges and equipment, drugs, or supplies were provided by Japan Society for the Promotion of Science. Samir Mitragotri reports a relationship with Liquideon LLC that includes: board membership and equity or stocks. Samir Mitragotri reports a relationship with Cage Bio that includes: board membership and equity or stocks. Samir Mitragotri reports a relationship with i2O Therapeutics that includes: board membership and equity or stocks. Samir Mitragotri reports a relationship with inTumo Therapeutics that includes: board membership and equity or stocks. Samir Mitragotri has patent licensed to PRESIDENT AND FELLOWS OF U.S. PATENT DOCUMENTS HARVARD COLLEGE, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials., Methods: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women., Results: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride., Conclusions: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing., (© 2024. The Author(s).)

Many chronic inflammatory diseases are attributed to disturbances in host-microbe interactions, which drive immune-mediated tissue damage. Depending on the anatomic setting, a chronic inflammatory disease can exert unique local and systemic influences, which provide an exceptional opportunity for understanding disease mechanism and testing therapeutic interventions. The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host-microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger nonresolving chronic inflammation, progressive bone loss, and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine (C-C motif) ligand 2 (CCL2) in murine ligature-induced PD using clinically relevant models as a preventive, interventional, or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment up-regulated M2-macrophage and downregulated proinflammatory and pro-osteoclastic markers. Furthermore, single-cell ribonucleic acid (RNA) sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting the triggering receptor expressed on myeloid cells-1 (TREM-1) signaling in classically activated macrophages and inducing protein kinase A (PKA) signaling in infiltrating macrophages. Finally, 16S ribosomal ribonucleic acid (rRNA) sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2-treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis., Competing Interests: Competing interests statement:The authors declare no competing interest.

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

Background: Periodontal diseases are associated with dysbiosis in the oral microbial communities. Managing oral biofilms is therefore key for preventing these diseases. Management protocols often include over-the-counter antimicrobial mouth rinses, which lack data on their effects on the oral microbiome's ecology, bacterial composition, metabolic activity, and dysbiosis resilience. This study examined the efficacy of antimicrobial mouth rinses to halt dysbiosis in in vitro oral biofilms under periodontitis-simulating conditions., Methods: Multispecies oral biofilms were grown on hydroxyapatite discs (HADs) and rinsed daily with one of six mouth rinses. Positive and negative controls were included. After three rinses, biofilms were analyzed with viability quantitative polymerase chain reaction and visualized using scanning electron microscopy. Supernatants of rinsed biofilms were used for metabolic activity analysis. In addition, human oral keratinocytes were exposed to rinsed biofilms to assess their inflammatory response. All outputs were analyzed for correlation using Spearman coefficient., Results: Product-related changes were observed in the rinsed biofilms. Three of the six tested mouth rinses could significantly prevent dysbiosis with ≥30% reduction in pathobiont abundance relative to the control. These biofilms had lower metabolic activity, and the exposed human oral keratinocyte produced less interleukin-8. Interleukin-8 production correlated to both pathobiont quantity and the metabolic activity of the biofilms., Conclusion: Some mouth rinses could support biofilm resilience and stop dysbiosis evolution in the biofilm model, with a clear product-related effect. Such mouth rinses can be considered for patients under maintenance/supportive periodontal therapy to prevent/delay disease recurrence. Others are more useful for different periodontal therapy stages., (© 2024 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)