The present study investigates clove oil nanoemulsion (CONE) as a novel therapeutic strategy against Streptococcus mutans-induced dental caries and periodontitis. CONE was formulated via ultrasonic emulsification, yielding a stable nanoemulsion with a mean droplet size of 44 ± 3.8 nm and a polydispersity index of 0.539. It exhibited potent, dose-dependent antibacterial activity with a minimum inhibitory concentration (MIC) of 0.4 mg/mL, a minimum bactericidal concentration (MBC) of 0.5 mg/mL, and a 25 mm inhibition zone at MIC in an agar diffusion assay. CONE significantly inhibited S. mutans biofilm formation by 82% and disrupted established biofilms with a 63% biomass reduction. Additionally, it was effective against co-species biofilms comprising Lactobacillus acidophilus and Candida albicans. Mechanistic studies revealed that CONE decreased extracellular polymeric substance production, reduced cell surface hydrophobicity (from 72% to 34%), and inhibited self-aggregation. It also suppressed glycolytic acid production and compromised acid tolerance. Furthermore, CONE induced oxidative stress, leading to lipid peroxidation and membrane damage, while exhibiting minimal cytotoxicity to human oral cells. It also showed enhanced antibacterial effects when combined with amoxicillin. These findings indicate that CONE is a promising alternative therapy for treating oral bacterial infections.

Dusquetide, a synthetic five-amino-acid peptide, represents a first-in-class therapeutic agent belonging to the family of Innate Defense Regulators (IDRs). Unlike conventional immunomodulators that often target specific cytokines or receptors, dusquetide exerts a broad spectrum of biological effects by selectively binding to the ZZ domain of the sequestosome-1 (SQSTM1/p62) protein, a pivotal signaling hub that integrates cellular responses to stress, infection, and inflammation. This interaction modulates the innate immune system, effectively resetting the balance between pro-inflammatory pathways and resolution-phase activities such as tissue repair and bacterial clearance without directly activating autophagy. Preclinical models have validated its efficacy across a diverse range of pathologies, including chemotherapy-induced oral mucositis, colitis, bacterial infections, and macrophage activation syndrome. Clinically, dusquetide has been evaluated most extensively in the context of head and neck cancer, where a Phase 3 trial (DOM-INNATE) demonstrated a biologically meaningful reduction in the duration of severe oral mucositis, although the primary endpoint did not achieve statistical significance in the intent-to-treat population, a discrepancy that has spurred detailed post-hoc analyses. More recently, the therapeutic potential of dusquetide has been expanded into the realm of orphan auto-inflammatory diseases. A pilot Phase 2a study in Behçet’s Disease (SGX945) published in late 2025 reported clinically meaningful reductions in the number, duration, and pain of both oral and genital aphthous ulcers, with a favorable safety profile. This comprehensive review synthesizes the current understanding of dusquetide’s molecular pharmacology, critically evaluates the aggregate clinical data across its lead indications, and discusses the future trajectory of this unique compound in addressing significant unmet medical needs in oncology supportive care and rare inflammatory disorders.

Periodontal disease (PD) is an established risk factor for rheumatoid arthritis (RA). The objective of this study is to identify how oral bacterial infections occurring in damaged periodontal tissue in PD can lead to joint inflammation and destruction in RA. Four separate commensal oral bacteria species were cultured with human neutrophils to induce neutrophil extracellular trap formation (NETosis). The resultant NETs contained neutrophil-derived peptidylarginine deiminase 4 (PAD4), which, within the NET milieu, became activated and mediated citrullination of both bacterial and neutrophil self-proteins. Citrullination was evaluated by adding rabbit anticitrulline antibody followed by Alexa Fluor 647-conjugated antirabbit IgG secondary antibody. Our data demonstrate that citrullinated oral bacteria induce Toll-like receptor 9 (TLR9)-spleen tyrosine kinase (Syk)-mediated human B cell activation, differentiation, proliferation, and antibody secretion, including the development of plasmablasts secreting anticitrullinated protein antibodies (ACPAs). Some ACPAs bind citrullinated oral bacteria to form immune complexes (ICs) that can activate monocyte-derived macrophages in vitro to differentiate into CD11b+CD64+ proinflammatory macrophages that secrete tumor necrosis factor and interleukin 6. In contrast, ACPA citrullinated-antigen complexes inhibit differentiation of antiinflammatory MerTKhiTREM2hiLYVE1hi macrophages that clear apoptotic cells and promote tissue repair. These data suggest ICs formed by ACPAs binding citrullinated antigens augment proinflammatory responses and inhibit antiinflammatory response. Our data support the hypothesis that in RA patients with PD, citrullinated oral bacteria breach damaged periodontal tissue to enter the circulation and induce both innate and adaptive proinflammatory responses that promote synovial tissue destruction.

The aim of this research is to evaluate the antimicrobial effectiveness of medicinal plant extracts (arak tree, clove oil and loan) against a group of clinically isolated tooth decay bacteria from some patients with tooth decay from different hospitals. The samples were collected and isolated and classified in the laboratory on the agar-maconkey and nutrient agar environments, which included bacteria that are affected by tooth decay (Staphylococcus, Streptococcus, Lactobacillus) and were identified and confirmed by chemo biotic tests. The plant extracts were prepared using ethanol extracts to evaluate their antibacterial activity using tablet diffusion in addition to measuring the minimum inhibitory concentration MIC at concentrations of 12, 25, 50 and 100 mg/ml, where the results showed that arac extract and clove oil had the highest antibacterial activity with observed inhibition regions against Streptococcus mutans Lactobacillus spp, while the effectiveness of the tablet fruit was relatively lower. It was also compared the effectiveness of plant extracts with a range of antibiotics. Some extracts have shown comparable effects of antibiotics against some bacteria. We conclude from this research that the use of natural extracts is effective and may contribute to the development of an alternative or complement to antibiotics for the treatment of tooth decay and oral bacterial infections.

Background/Objectives: The rapid emergence of antibiotic-resistant oral pathogens has rendered many conventional therapies increasingly ineffective. Antimicrobial peptides (AMPs) have emerged as a promising therapeutic alternative due to their unique mechanisms of action and low propensity for inducing resistance. The delivery of novel therapeutic AMPs against oral cavity bacterial infections requires effective pharmaceutical dosage formulations. This study investigated the potential of two liposomal formulations for the association and delivery of the antimicrobial peptide (AMP) LL17-32 against the dental bacterial pathogen Porphyromonas gingivalis. Methods: Liposomes composed of either negatively charged soya lecithin (SL) or neutrally charged dioleoyl-phosphatidylcholine (DOPC) phospholipids were formulated and characterized based on their hydrodynamic size distribution, ζ-potential, morphology, membrane fluidity, peptide association efficiency, stability and release of peptide in vitro under physiological conditions. The characterization of their biological activity included efficiency of bacterial killing, bacterial adherence, and mammalian cell cytotoxicity using human gingival keratinocyte (TIGK) cells. Results: Both liposomal formulations exhibited spherical morphology with hydrodynamic diameters smaller than ~170 nm and demonstrated good colloidal stability. LL17-32 showed high association efficiency with both liposomal membranes, with no detectable LL17-32 in vitro release. In biological assays, peptide-loaded DOPC liposomes exhibited dose-dependent bactericidal activity against P. gingivalis, whereas SL liposomes significantly attenuated the bactericidal effect of LL17-32. Both formulations displayed reduced cytotoxicity toward human gingival keratinocyte (TIGK) cells versus free peptide. Conclusions: These findings suggest that DOPC liposomes represent a promising delivery system for LL17-32 by adhering to P. gingivalis and exhibiting minimal cytotoxicity to mammalian cells. This study emphasises the critical role of lipid charge in designing AMP delivery systems for antibacterial applications, while it additionally demonstrates the utility of flow cytometry as a quantitative tool to assess liposome–bacteria association.

Cases of focal oral bacterial infections - including infective endocarditis - have been reported during orthodontic treatment in patients with no previous medical history. This raises the question of whether orthodontic treatment is responsible for the development of these infections. The aim of this narrative literature review was to determine whether or not bacteremia, directly or indirectly related to orthodontic treatment, is present and what precautions should be taken in orthodontic treatment of patients with and without risk of infective endocarditis. A narrative literature review was carried out using two keyword searches on PubMed. Transient bacteremia may occur during everyday activities and dental procedures. This bacteremia is influenced by factors linked to the invasiveness of the procedure and the patient's periodontal indices. In patients at risk of infective endocarditis, the new French professional recommendations do not contraindicate any orthodontic procedure. In patients at high risk of infective endocarditis, stripping, corticotomies, orthodontic exposure of impacted teeth, and insertion and removal of bone anchors require antibiotic prophylaxis. The following procedures are contraindicated in these patients: pulpectomy of temporary teeth, pulp capping of mature permanent teeth, use of bone regeneration membranes, and conservative treatment of peri-implantitis. Any procedure, whether therapeutic or not, generates bacteremia, which is often minimal and depends on the procedures performed. Orthodontic appliances, because of the length of time they are worn and the difficulty of maintaining good oral hygiene, are likely to generate an additional bacteremia which, in principle, should have no consequences in a healthy patient. Although orthodontic procedures are relatively frequent, studies are rare and often have a low level of evidence. The role of the orthodontist is to identify the patient's level of risk, to educate and motivate the patient in oral hygiene, and to apply the precautionary measures set out in the new HAS recommendations for patients at risk of infective endocarditis.

Objective: The present study sought to investigate the frequency of halitosis in a sample of smokers and non-smokers and the association of smoking and perceived oral bacterial infections. Material and Methods: A questionnaire was administered to 301 respondents. The structured questionnaire included demographics, oral hygiene behaviors, medical and dental history, lifestyle behaviors, awareness of halitosis and its social consequences in others. Statistical analyses were performed with chi-square tests to identify any associations of halitosis and possible risk factors. Results: Among respondents, 22.9% self-reported using tobacco products while 63.4% self-reported experiencing halitosis sometimes or frequently. Smoking, periodontal disease, dental caries, poor clinical hygiene (not brushing, not flossing or using mouthwash) and some systemic diseases were related to self-reporting halitosis (P < 0.01). Only 9.6% of respondents accessed treatment. Most respondents (86%) realized their halitosis themselves rather than it being diagnosed professionally. Conclusion: This study provides insight into the relationship between smoking and self-reported halitosis and the need for greater awareness and tailored public health initiatives.

Introduction: Infective endocarditis (IE) is a heart condition that may result from subacute bacterial infections. One cause of IE is oral bacterial infections, particularly Streptococcus species, which enter the blood vessels through injured gingiva during tooth brushing or dental procedures. Rheumatic heart disease (RHD) is a major predisposing factor in developing countries, with viridans streptococci implicated in its etiology. This background highlights the importance of maintaining oral hygiene, especially in RHD patients, to reduce the risk of IE. This systematic review aims to investigate the association between poor oral hygiene and the risk of IE in patients with RHD. Method: A systematic review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles published between 2014 and 2024 were sourced from PubMed, Scopus, and Google Scholar using specific keyword combinations related to IE, RHD, and oral health. Inclusion and exclusion criteria were applied based on the PECO framework. Results: A total of four eligible studies were identified. The findings suggest that RHD patients with poor oral hygiene are more vulnerable to developing IE due to an increased risk of bacteremia originating from oral infections. Conclusion: Poor oral hygiene is associated with an increased risk of infective endocarditis in patients with rheumatic heart disease. Bacteria adhering to heart valves form biofilms and cause vegetations on the tissue. Preventive dental care and prophylactic measures should be emphasized in this high-risk population.

In light of the growing issue of antibiotic resistance, this study explored phage encapsulation within lactose particles for potential use in treating oral and ear bacterial infections. Firstly, phage-loaded suspensions that ensured phage stability at RT for 24 h were developed. After electrospraying, phage-loaded particles were successfully generated with an encapsulation efficiency (EE) of 31 % at a phage stock concentration of 50 % v/v. The phage titer decreased only slightly from 5 × 10 7 PFU/mg to 1.5 × 10 7 PFU/mg after processing, maintaining the same order of magnitude. The particles exhibited spherical morphology and successful phage encapsulation, with a burst release of phages within 10 min of immersion in an aqueous medium (99.0 ± 6.9 %). The phage-loaded particles demonstrated enhanced antibacterial efficacy compared to pure phage solutions, completely inhibiting P. aeruginosa growth for over 24 h at a particle concentration of 20 mg/ml, likely due to a high localized phage concentration. Stability studies indicated that phages remained viable at various temperatures, with greater stability at lower temperatures (4 °C, and −20 °C), though phage activity gradually decreased over time in particle form, particularly at room temperature.

Aged garlic extract (AGE) has been reported to exert anti-inflammatory effects. AGE has been recently found to reduce the inflammatory symptoms of periodontitis, a widespread chronic inflammatory disease caused by oral bacterial infection. However, the mechanisms underlying these effects remain unclear. In the present study, it was aimed to determine the effects of AGE on experimental periodontitis and the related inflammatory factors. AGE (2 g/kg/day) was orally administered to 15 mice during the experimental period, while a control group consisted of 15 mice that received pure water. A total of 3 days after initiation of administration, the left maxillary second molar was ligated with a 5-0 silk thread for 7 days. Blood biochemical tests were performed to monitor the systemic effects of AGE. Alveolar bone loss was measured morphometrically using a stereomicroscope, and reverse transcription-quantitative PCR was performed to assay mRNAs of proinflammatory cytokines in gingival tissues. A histological survey was also performed to identify osteoclasts in periodontitis lesions (five mice per group). The total protein and albumin levels showed no significant differences between the AGE and control groups. However, ligation-induced bone resorption was lower in the AGE group than in the control group (P=0.01). Additionally, ligature increased the mRNA expression of inflammatory cytokines, whereas AGE administration tended to suppress them. Remarkably, tumor necrosis factor gene expression was significantly suppressed (P=0.04). The number of osteoclasts in periodontitis lesions was reduced in the AGE-treated group. These results indicate that AGE prevents alveolar bone loss by suppressing the inflammatory responses related to osteoclast differentiation in the periodontal tissue. Further research is needed to elucidate the role of AGE in reducing inflammatory bone resorption.

Abstract Dental caries is a common chronic disease affecting tooth of many subjects at different ages due to biofilm-mediated oral bacterial infection. Streptococcus mutans is regarded as a pivotal cariogenic bacterium responsible for dental caries and plaque formation. It produces exopolysaccharides on the surface of the tooth promoting the colonization of cariogenic bacteria and dental biofilm development. Formation of this biofilm can be prevented by using different antimicrobial agents such as BlueM mouthwash, polypyrrole, natural flavonoids, and endocannabinoid anandamide.

ObjectivesThis study aimed to investigate the potential role of Enterococcus faecalis in the development of atherosclerosis, focusing on two primary mechanisms: the induction of vegetative endocarditis and the promotion of oxidative stress. By examining systemic effects following dissemination of E. faecalis, commonly associated with dental infections, the study sought to explore its possible contribution to cardiovascular pathology. MethodsE. faecalis was isolated from dental caries lesions and identified as gram-positive cocci using selective and differential culture media. Twenty adult albino rats were randomly divided into two groups (n=10 per group). Group 1 served as the control, while Group 2 received an intraperitoneal injection of E. faecalis suspension (1 mL, 7.8 × 10⁷ CFU/mL). After 90 days, oxidative stress biomarkers—GSH, SOD, TAC, MDA, NO, IL-6, and TNF-α—were measured in cardiac and aortic tissues. Serum CRP levels were assessed to evaluate systemic inflammation. Histopathological examinations of the aorta and heart were conducted to assess structural and inflammatory changes. ResultsInfected rats exhibited significant histopathological alterations in the aorta, including lipid vacuole accumulation, foam cell infiltration in intima and media layers, and fragmentation of elastic fibers. Cardiac examination revealed vegetative endocarditis with bacterial colonies, mononuclear cell infiltration, myocardial fatty degeneration, and mural valve thrombi. Coronary arteries displayed wall thickening, thrombus formation, and periarteritis. Biochemical assays showed elevated oxidative stress markers and significantly increased CRP levels in Group 2 compared to controls. ConclusionThe findings suggest that systemic E. faecalis infection can contribute to atherosclerosis by promoting both vegetative endocarditis and oxidative stress. This supports a mechanistic link between oral bacterial infections and cardiovascular disease, underscoring the importance of oral health in systemic disease prevention.

Background/Objectives: Bacterial infections in the oral cavity and outer ear require effective and targeted drug delivery systems. This study details the production of drug-loaded lactose microparticles, with the aim of creating antibiotic formulations for ultimate use in combatting oral and outer ear bacterial infections. Methods: Lactose particles were prepared via spray drying and optimized with varying ciprofloxacin (cipro) loadings to maximize the drug content. The particles were characterized to evaluate their performance in terms of physicochemical properties, drug-loading efficiency, drug-release kinetics, and antibacterial activity. Results: The resulting particles exhibited spherical morphology, efficient cipro loading (in the range of 1.1-52.9% w/w) and rapid cipro release within 5 h (achieving 70-81% release). In addition, they demonstrated effective concentration-dependent antibacterial activity against gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa, with bacterial growth effectively inhibited for more than 24 h when particle concentrations reached the minimum inhibitory concentration. Conclusions: These findings highlight the potential of spray-dried cipro loaded lactose particles as an efficient approach for localized antibacterial treatment, offering a promising solution for managing bacterial infections in the oral cavity and outer ear.

Pathogens exert strong selection on hosts that evolve and deploy different defensive strategies, namely minimizing pathogen exposure (avoidance), directly promoting pathogen elimination (resistance) and/or managing the deleterious effects of illness (disease tolerance). However, how the host response partitions across these processes has not been directly tested in a single host-pathogen system, let alone in the context of known adaptive trajectories resulting from experimental evolution. Here, we compare a Drosophila melanogaster population adapted to oral infection with its natural pathogen Pseudomonas entomophila (BactOral), to its control population to find no evidence for behavioural changes but measurable differences in both resistance and disease tolerance. In BactOral, no differences were detected in bacterial intake or defecation, nor gut cell renewal. However, a measurable relative decrease in bacterial loads correlates with an increase in gut-specific anti-microbial peptide production, pointing to a strengthening in resistance. Additionally, we posit that disease tolerance also contributes to the response of BactOral through a tighter control of self- and pathogen-derived damage caused by bacteria exposure. This study reveals a genetically complex and mechanistically multi-layered response, possibly reflecting the structure of adaptation to infection in natural populations.

The "gut-brain axis," a bidirectional communication system between the gastrointestinal tract and the central nervous system, plays a crucial role in regulating complex physiological functions in response to nutrients, pathogens, and microbiota. However, the cellular and molecular mechanisms governing this regulation remain poorly understood. Using Drosophila melanogaster as a model organism, we previously identified NP3253 neurons, located in both the brain and gut, as key contributors to gut homeostasis during oral bacterial infection. Here, we found a novel role of NP3253 neurons in regulating starvation resistance. We observed that a subset of NP3253 neurons in the gut were activated during starvation. To investigate downstream effect, we conducted RNA-Seq analysis on the gut of adult flies with genetically silenced NP3253 neurons, comparing gene expression under starved and fed conditions. This analysis identified 26 genes differentially expressed in response to both starvation and NP3253 neuronal activity. Among these, CG12643, encoding an uncharacterized short peptide, was found to be essential for starvation resistance in the gut. Our findings demonstrate that NP3253 neurons modulate the gut gene expression in response to starvation, thereby supporting physiological adaptation to environmental stressors.

ABSTRACTDental caries represents one of the most widespread oral bacterial infections, affecting billions of individuals worldwide and presenting significant public health challenges. Effective diagnosis and treatment are hindered by the limitations of traditional clinical treatment methodologies, which often involve laborious examinations and invasive procedures. In this study, we employ an aggregation‐induced emission probe, MeOTpy, for instant molecular detection and photodynamic treatment of dental caries. MeOTpy interacts specifically with cariogenic bacteria, exhibiting bright fluorescence upon binding to bacteria and generating reactive oxygen species under white light irradiation. This aggregation‐induced photosensitivity enables rapid assessment of carious disease through fluorescent detection in dental plaque samples, facilitating easy identification of lesion sites in decayed teeth treated with MeOTpy. Furthermore, photodynamic inhibition of cariogenic biofilms is achieved by culturing ex vivo biofilms isolated from children with severe early childhood caries. MeOTpy also effectively prevents dental caries while preserving oral microbial diversity in a cariogenic infection model on rat pups. This study presents an integrated strategy for the precise diagnosis and treatment of dental caries at the point of care.

Oral infections exhibit variability in their causative agents and clinical presentations, underscoring the necessity of accurate diagnosis for effective management. Despite extensive documentation globally, data on these infections from Brazil remain scarce. This study aimed to assess the occurrence, clinical features, and differential diagnosis of oral viral, fungal, and bacterial infections at a single center in southern Brazil. A retrospective analysis was conducted between 2010 and 2023. Clinicodemographic data, comorbidities, and routine medication use were analyzed descriptively and statistically. A total of 462 cases were included. The median age was 49.5 years (range: 2-100). Viral infections were the most frequent (65.8%), with squamous papilloma accounting for 49.4% of cases. Fungal infections comprised 29.4% of cases, predominantly erythematous candidiasis (20.8%) and pseudomembranous candidiasis (5.6%). These infections were more common in women, older adults (p<0.001), and individuals with comorbidities such as systemic arterial hypertension (p=0.006) and diabetes mellitus (p=0.028). Bacterial infections were rare (4.8%), with actinomycosis being the most frequent (2.2%). Data from our series on oral viral, fungal, and bacterial infections align with the literature. The results emphasize the importance of tailored diagnostic approaches, particularly for at-risk patient populations. Key words:Bacterial infections, Communicable diseases, Mycoses, Oral manifestations, Virus diseases.

Porphyromonas gingivalis is widely recognised as a periodontal pathogen. In recent years, there has been growing interest in the use of medicinal plant extracts as alternative treatments for periodontitis to combat the emergence of antibiotic-resistant bacteria. Ruta angustifolia L. Pers has been traditionally used to treat various ailments, including oral bacterial infections. However, the antimicrobial potential of R. angustifolia extracts against the periodontal pathogen P. gingivalis remains unexplored. Hence, the aim of this study was to investigate the antimicrobial activity of R. angustifolia extracts against P. gingivalis. The antimicrobial activity of R. angustifolia extracts (crude methanol, hexane and chloroform fractionated extracts) against P. gingivalis was evaluated using the well diffusion method. Additionally, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. Biofilm biomass assessment and live/dead cell viability assays were performed to analyse the effect of R. angustifolia extracts. Ultrastructural morphological changes in P. gingivalis cells were determined using field emission scanning electron microscopy (FE-SEM). It was found that P. gingivalis was susceptible to R. angustifolia extracts, with the chloroform fractionated extract exhibiting the highest inhibition zones. The MIC and MBC of chloroform fractionated extract were determined to be 6.25 mg/mL which substantially reduced P. gingivalis biofilm biomass. Live/dead cell viability assays showed the highest percentage of dead P. gingivalis cells after 48 h of incubation. FE-SEM confirmed that the chloroform fractionated extract effectively damaged the bacterial cell wall and altered the ultrastructural morphology of P. gingivalis. The results indicated that extracts of R. angustifolia has the potential to be used as an alternative treatment in addition to conventional periodontal therapies.

Periodontitis is a chronic inflammatory disease triggered by oral bacterial infection, with the bacterium Porphyromonas gingivalis being a major causative agent. The association between periodontitis and various systemic diseases has been demonstrated. Recent research has also highlighted the relationship between the aggravation of maternal periodontitis and adverse pregnancy outcomes such as preterm birth and low birth weight. However, the molecular mechanisms underlying how factors from periodontitis influence pregnancy and fetal development remain unclear. Extracellular vesicles (EVs) are nano-sized spherical particles secreted into the tissue microenvironment by various types of cells. EVs have garnered interest in recent years due to their role in intercellular communication. In the present study, we investigated whether EVs derived from P. gingivalis–infected macrophages (Pg-inf EVs) reach the feto-placental unit and influence fetal development. Through a series of in vivo experiments in mice, we demonstrated that Pg-inf EVs translocated to the feto-placental unit and impaired fetal development in size and weight. Histological analysis revealed disoriented blood vessel alignment and impaired angiogenesis in the placentas of Pg-inf EV–injected groups, indicative of compromised placental function. Proteome analysis revealed a significant decrease in Vegfr1 expression in the placentas of the experimental group. Moreover, Pg-inf EVs reduced VEGFR1 expression in cultured human vascular endothelial cells, highlighting a potential molecular mechanism through which these EVs exert their effects on placental angiogenesis. This is the first study to reveal a novel pathway in which oral bacteria–infected macrophage EVs in maternal periodontitis affect pregnancy via the feto-placental unit.

Background: Areca nut (Areca catechu L.) and red ginger (Zingiber officinale Rosc. var. rubrum) are herbal plants that have specific phytochemical compound functional groups that have the potential to be used as antifungal and antibacterial. However, the optimal effect of the combination of the two extracts against oral candidiasis and oral bacterial infections is not yet known with certainty. This study aims to evaluate the effect of the combination of areca nut and red ginger on the development of microbial infection in oral cavity. Methods: Plant extraction is carried out using the maceration method. Functional group test using an FTIR spectrophotometer. The antifungal assay with Candida albicans (C. albicans) ATCC 10231 using well-diffusion technique on sabouraud dextrose agar media. Comparison of concentrations of areca nut: red ginger combination is 80%:20%, 50%:50%, and 20%:80%, respectively. The disc diffusion method was used to determine the antimicrobial activities against Staphylococcus aureus (S. aureus). Data analysis of antifungal assay was carried out using the Kruskall-Wallis test with p&lt;0.05, post-hoc using the Mann-Whitney test, and the antibacterial activity using one-way ANOVA with p&lt;0.05 and post-hoc using LSD test. Results: The areca nut extract confirmed the presence of the phenolic, alcohol, and aromatic benzene compounds. The red ginger contained flavonoid, alkaloid, and aromatic functional groups. The combination of areca nut and red ginger extract with a concentration ratio of 80%:20% had the highest inhibitory activity against C. albicans; 15.13±1.71mm with the positive control being 12.43±1.40 mm. In the antibacterial activity, the combination of 80%:20% areca nut and red ginger extract has an average inhibition zone of 12.43±1.40 mm which is the strongest inhibition ability while the positive control is 11.21±2.62 mm. Conclusion. The combination of areca nut and red ginger extracts contained potential phytochemical compounds that influence the antimicrobial ability. The concentration ratio of 80%:20% of areca nut and red ginger extract has the strongest inhibitory activity against C. albicans and S. aureus.