Je-Hyun Eom

Halitosis affects a substantial proportion of adults worldwide, yet the compositional and functional basis of the oral microbiome in halitosis remains incompletely understood, particularly in East Asian populations. We performed 16S rRNA gene amplicon sequencing of oral gargle samples from 45 individuals with halitosis and 45 healthy controls in South Korea, generating approximately 4,600 amplicon sequence variants. Beta diversity analysis revealed significant community-level separation (PERMANOVA, P = 0.001) and an elevated Firmicutes/Bacteroidota ratio in halitosis, although alpha diversity did not differ between groups. Because the halitosis group was significantly older than controls, age-adjusted PERMANOVA and age-matched sensitivity analyses confirmed that separation persisted independent of age (age-adjusted R ² = 0.030, P = 0.003). Halitosis-associated microbiomes were enriched for Prevotella melaninogenica and Peptostreptococcus stomatis , whereas healthy microbiomes were distinguished by Haemophilus parainfluenzae and Veillonella rogosae (LEfSe). Functional profiling using PICRUSt2 revealed a counterintuitive, predicted suppression of sulfur metabolism in halitosis: pathways for sulfate assimilation, cysteine, and methionine biosynthesis were predicted to be significantly reduced relative to healthy controls. This predicted shift was significantly inversely correlated with directly measured volatile sulfur compounds (H₂S and methyl mercaptan; Spearman ρ = −0.54 and −0.64, both P < 0.0001), providing phenotypic support for the predicted signature. These findings suggest healthy oral microbiomes efficiently channel sulfur into anabolic pathways, whereas dysbiotic microbiomes may lose this capacity, allowing volatile sulfur compounds to accumulate. Our study provides a species-resolved, functionally annotated reference framework for halitosis-associated oral dysbiosis in a Korean cohort, and identifies candidate targets for diagnosis and intervention. IMPORTANCE: Halitosis (bad breath) affects up to 30% of adults worldwide and is caused by volatile sulfur compounds (VSCs) produced by oral bacteria, yet the underlying microbial mechanisms remain poorly understood. Our study of 90 Korean adults reveals that halitosis is associated not only with an overgrowth of Prevotella species but also with a predicted, paradoxical suppression of the microbial community’s capacity to assimilate sulfur into anabolic biosynthetic pathways. This predicted “sulfur assimilation failure” was associated with elevated VSC accumulation, supporting a reframing of halitosis as a community-level metabolic dysfunction rather than simple bacterial overproduction. These findings have direct clinical implications: the identified Prevotella -dominated dysbiosis and associated sulfur pathway signatures represent candidate biomarkers for objective halitosis diagnosis, and the restoration of microbial sulfur-channeling capacity offers a rational target for probiotic and prebiotic interventions. This work also contributes a well-characterized oral microbiome reference data set from an underrepresented East Asian population.

Background: Non-invasive molecular tools that can both screen for severe periodontitis and quantify treatment-associated pathogen changes remain an unmet need. We evaluated a non-invasive multiplex quantitative polymerase chain reaction (qPCR) mouthwash panel providing absolute colony-forming-unit (CFU) quantification of five periodontal pathogens ( Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Prevotella intermedia, Fusobacterium nucleatum ), and asked whether a single test can both screen for severe disease and track each patient’s species-level treatment response. Methods: Treatment-response monitoring was assessed in a real-world retrospective cohort (349 patients, 703 visits; 235 paired pre/post-treatment samples) using paired Wilcoxon signed-rank tests and Jonckheere–Terpstra trend tests across baseline stage. Screening performance was independently evaluated in a prospective cross-sectional cohort (n=87; 31 healthy, 56 Stage III/IV) with leave-one-out cross-validation (LOOCV) and a pre-specified sensitivity analysis. Results: For screening, LOOCV AUC was 0.96 for P. gingivalis and 0.97 for the combined panel, preserved under inclusion of antibiotic- and treatment-exposed subjects. Beyond screening, the panel resolved each patient’s species-level response to non-surgical therapy: all five species decreased significantly, with median within-patient reductions of −0.37 to −0.72 log ₁₀ CFU (paired Wilcoxon, all pF. nucleatum reached or fell below the Healthy reference median in 61% of evaluable patients, whereas P. gingivalis reached it in only 5% and remained approximately 500-fold above the Healthy reference at the median final visit, identifying residual keystone-pathogen burden not captured by clinical or radiographic assessment. Conclusion: In this two-cohort evaluation, a single non-invasive mouthwash qPCR test provided two linked clinical outputs: high-accuracy screening for severe periodontitis and quantitative individual-level tracking of species-specific microbial response to therapy. These findings are preliminary, derive from a single-center screening cohort and a retrospective monitoring cohort, and require external validation before clinical deployment. By placing pathogen loads on the same absolute CFU scale, the assay supports both cross-sectional disease detection and longitudinal residual-burden monitoring as an adjunct to the 2018 AAP/EFP framework. Clinical Research Information Service (CRIS) registration: KCT0011511 ( https://cris.nih.go.kr ).

Objectives: This pilot trial evaluated the adjunctive effects of combined Lacticaseibacillus rhamnosus DM163 and Lactobacillus plantarum DSR920 following scaling and root planing (SRP) on periodontal parameters, oral microbiota, and safety in patients with mild gingivitis. Methods: Thirty participants with mild gingivitis were enrolled in this single-center, double-blind, randomized pilot trial. After SRP, the participants received either probiotics or a placebo for 12 weeks. Clinical parameters, oral bacteria detected by qPCR, serum inflammatory biomarkers, and safety outcomes were assessed. Results: Twenty-seven participants were included in the analysis (test group n=14, placebo group n=13). No statistically significant between-group or within-group changes were observed in any of the clinical periodontal parameters. Treponema denticola increased in the 6-week mouthwash samples in the placebo group (p=0.005), while Fusobacterium nucleatum increased in the 12-week plaque samples in the test group (p=0.009). Overall, no consistent reduction in major periodontal pathogens was observed. Most serum inflammatory biomarkers remained below the detection limits, and no serious adverse events occurred. Conclusions: In the present post-SRP mild gingivitis setting, the adjunctive use of probiotics was well tolerated but did not demonstrate statistically significant clinical or microbiological effects. Future trials should optimize baseline standardization and statistical power, and incorporate gingival crevicular fluid analysis. Trial registration: KCT0009762.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is closely associated with obesity, insulin resistance, and gut microbiota dysbiosis. This study investigated the effects of a probiotic combination of Lactiplantibacillus plantarum DM083 and Lacticaseibacillus rhamnosus DM163 on glycemic control, insulin resistance, gut microbiota composition, and metabolic parameters in high-fat-diet (HFD)-induced obese mice. Methods: Male C57BL/6 mice were fed a 60% HFD for 8 weeks and subsequently administered DM083/163 (1 × 10⁹, 5 × 10⁹, or 1 × 10¹⁰ CFU/day) or metformin (250 mg/kg/day) for 12 weeks. Glucose metabolism, insulin resistance, hepatic gene expression, gut microbiota composition, and fecal short-chain fatty acids (SCFAs) were evaluated. Results: DM083/163 supplementation at 1 × 10¹⁰ CFU/day significantly reduced fasting blood glucose, HbA1c, oral glucose tolerance test area under the curve, and HOMA-IR compared with the HFD control group (p < 0.05). Hepatic expression of the gluconeogenic genes Pck1 and G6pc was significantly downregulated, accompanied by reduced hepatic and serum TNF-α levels. Gut microbiota analysis revealed significant overall differences in beta diversity across groups (PERMANOVA, R² = 0.262, p = 0.001), driven primarily by diet, with a trend toward a reduced Bacillota/Bacteroidota ratio in the high-dose group. Conclusions: DM083/163 supplementation improved glycemic control and insulin resistance in HFD-induced obese mice. These effects were associated with suppression of hepatic gluconeogenesis, attenuation of inflammation, and increased SCFA production, findings that are consistent with, but do not establish, modulation of the gut–liver axis. These findings support the potential use of DM083/163 as a probiotic intervention for obesity-associated T2DM.

Background/Objectives: Forest therapy has demonstrated stress-reducing and immune-enhancing effects, yet its simultaneous impact on cognitive function, stress biomarkers, and oral microbiota in older adults remains unexplored. This study aimed to evaluate the effects of an 8-week community-based village forest experience program on cognitive function, salivary cortisol, and oral pathogenic bacteria in community-dwelling older adults. Methods: A total of 125 older adults (mean age 82.2 ± 5.3 years; 87.2% female) from 17 senior centers participated in a single-arm, pre–post intervention study. Cognitive function was assessed using the Cognitive Impairment Screening Test (CIST), salivary cortisol was measured by ELISA, and seven oral bacterial species were quantified by qPCR. Results: CIST scores improved significantly (p = 0.003, d = 0.27), with the suspected cognitive impairment subgroup showing greater improvement (d = 0.66) and 48.8% transitioning to normal classification. Salivary cortisol decreased significantly (p = 0.002), and total bacterial load, Porphyromonas gingivalis, and Tannerella forsythia were significantly reduced. The 80–84-year age group showed the greatest cognitive gain, whereas participants aged 85 and older showed no significant change. Conclusions: An accessible village forest program may simultaneously benefit cognitive function, stress, and oral health in older adults with early-stage cognitive decline. Controlled studies are needed to confirm causality and elucidate the underlying mechanisms.

Background/Objectives: Alzheimer’s disease (AD) exhibits high heritability (60–80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean Chip v2.0 genotyping (~1.2 M SNPs) and Illumina EPICv2 DNA methylation profiling. Genetic burden score (GBS) was calculated by summing risk alleles across 320 variants in six AD-associated genes (APOE, PICALM, CLU, CR1, BIN1, and ABCA7). Results: An unexpected pattern was observed in this family: the affected individual (J-003) had the lowest GBS (39 alleles), while individuals with higher genetic burden (51–61 alleles) remained cognitively healthy. J-003 also exhibited lower APOE methylation (β = 0.495) compared to the family mean (β = 0.523). CR1 contributed the most risk alleles across the family, followed by PICALM. Conclusions: This single-case observation cannot establish causality, generalizability, or biological significance. The affected individual’s lower APOE methylation may represent a causal factor, disease consequence, or coincidental variation—scenarios that cannot be distinguished from this dataset. Validation in larger cohorts with multiple affected individuals is required to determine whether integrated multi-omics approaches can inform personalized risk assessment in familial contexts.

Eun-Mi Choi, Mu-Yeol Cho, Je-Hyun Eom, Ji-Won Kim, Ji-Young Hwang, Hye-Sung Kim. J Dent Hyg Sci 2025;25:256-66. https://doi.org/10.17135/jdhs.2025.25.3.256

SUMMARY: Recent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome’s role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.

Objectives: Probiotic supplementation, integrated into routine oral care, may improve periodontal status and metabolic function. In this retrospective longitudinal study, we evaluated the efficacy of probiotics added to non-surgical periodontal treatment (NSPT) in reducing the burden of oral pathogens and improving metabolic dysfunction. Methods: Twenty outpatients with chronic periodontitis and at least one metabolic abnormality underwent NSPT with daily probiotic supplementation for 12 weeks. Baseline and post-intervention assessments included clinical indices, blood pressure, and blood biomarkers (HbA1c, fasting glucose, and lipid profiles), with analysis of oral pathogens using qPCR. Results: Among the 13 eligible participants, probiotics with NSPT resulted in significant reductions in HbA1c (-0.3%, p<0.001), and systolic blood pressure (-9.6 mmHg, p<0.001), and Tannerella forsythia (p<0.05) levels, along with decreasing trends in other pathogens. However, no significant changes were noted in periodontal indices, including probing pocket depth and bleeding on probing, nor in lipid profiles. Conclusions: These f indings suggest that probiotic supplementation with NSPT may improve glycemic control and systolic blood pressure but may have a limited effect on periodontal indices, warranting larger trials to confirm its potential.