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.

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.

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

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: 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 p<0.001) and reduction magnitude scaling with baseline severity. This response was strongly species-specific and clinically informative at the individual level: In the implant-bearing high-baseline-burden subgroup, post-treatment F. 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 ).