Periodontitis, a leading cause of tooth loss worldwide, arises from a dysregulated host immune response, and males consistently show higher prevalence and more severe disease than females. This disparity historically has been attributed to behavioral/environmental factors, but growing evidence indicates that biological sex, acting through hormonal signaling and sex chromosome–linked genetic mechanisms, independently shapes periodontal immune responses and subsequent bone resorption. In this review, we examine preclinical and clinical evidence on the impact of biological sex on host modulation therapies to prevent periodontitis. The IL-1β/inflammasome pathway and osteoclast differentiation via receptor activator of nuclear factor–κB ligand (RANKL)/osteoprotegerin (OPG) signaling both show clear sex-dependent regulation in experimental periodontitis, illustrating the biological complexity that single-target therapies must address in this heterogeneous condition. In a mouse model, inflammasome-mediated IL-1β signaling drives alveolar bone loss selectively in males, while females progress to comparable bone loss through IL-1β–independent mechanisms. IL-17 plays a dual role, driving inflammatory bone resorption while also supporting antimicrobial defense, and evidence points to this balance being sex dependent, with more severe effects observed in females when IL-17 signaling is disrupted. IL-6 is an established driver of periodontal bone loss, and although sex-specific data within periodontitis remain limited, sex-dependent anti–IL-6 receptor treatment responses have been observed in other inflammatory diseases that warrant further investigation. Complement-mediated immunity shows biological sex differences in humans and animal models, though whether these discrepancies directly influence periodontal disease progression needs to be determined. Resolvins and cyclooxygenase inhibitors also show sex-dependent effects outside the periodontal field. Collectively, this evidence positions biological sex as a tractable, currently underappreciated variable to improve host modulation strategies. Incorporating sex as a biological variable into preclinical and clinical periodontal research and ensuring sex-disaggregated data reporting offer a clear opportunity to develop precise, sex-informed nonsurgical therapeutics that better serve both male and female patients.
Community water fluoridation (CWF) is an effective public health intervention to prevent dental caries. This study investigated potential associations between lifetime fluoride exposure from CWF and cognitive outcomes in older Irish adults and whether early-life exposure modified these associations. Data from the Irish Longitudinal Study on Ageing (TILDA; wave 3, 2014 to 2015) were analyzed ( n = 6,684). Lifetime (≥50 y) and early-life (ages 0 to 5 y) fluoride exposures were estimated by linking residential histories to national water fluoride monitoring data and were available for N = 2,495 participants (mean age 65.32 y, standard deviation 8.64 y). Primary exposures were cumulative lifetime exposure to fluoridated water (CLEFW; continuous) and percentage lifetime exposure to fluoridated water (%LEFW), classified as low (<25%), medium (25% to 75%), or high (>75%). Cognitive outcomes were Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) error scores (30 minus raw scores), with higher scores indicating poorer cognition. Associations were examined using multivariable negative binomial regression models, adjusted for sociodemographic, lifestyle, health, loneliness, and health care access factors. Effect modification by early-life fluoride exposure (any/none) was tested using interaction terms. CLEFW showed no association with cognitive errors (incidence rate ratio [IRR] MMSE = 1.00, 95% confidence interval [CI]: 0.99 to 1.01; IRR MoCA = 1.00, 95% CI: 1.00 to 1.01). In unadjusted models, the high-exposure %LEFW group had lower cognition errors than the low-exposure reference group (IRR MMSE = 0.62, 95% CI: 0.49 to 0.79; IRR MoCA = 0.72, 95% CI: 0.62 to 0.83), but these became nonsignificant in fully adjusted models (IRR MMSE = 1.17, 95% CI: 0.88 to 1.56; IRR MoCA = 1.10, 95% CI: 0.94 to 1.29). There was no evidence of effect modification by early-life fluoride exposure for either cognitive outcome ( p interaction > 0.05). Lifetime fluoride exposure from CWF was not associated with later-life cognitive function in older Irish adults, and there was no statistical evidence of effect modification by early-life exposure.
The integration of artificial intelligence (AI), particularly large language models and agentic pipelines, is reshaping dental research. This article examines the opportunities and risks of AI in knowledge production in oral health research. On one hand, AI accelerates literature synthesis, data analysis, and manuscript drafting; on the other, it introduces new risks, including fabricated findings and citations, overconfident inference, and homogenization of research focus. These shifts challenge the mechanisms that maintain scientific credibility such as peer review, reproducibility, and human judgment, especially in fields like dentistry, where small datasets and limited editorial capacity may amplify vulnerabilities. We here identify 3 structural asymmetries: 1) the growing gap between the rapid pace of AI-assisted production and slow human validation, 2) the divergence between AI-generated linguistic fluency and the true robustness of the generated evidence, and 3) unequal institutional capacity to govern AI and the incentives set by the research system for (mis)using AI for research. We conclude with a call for proportional and enforceable governance frameworks, including mandatory AI disclosure standards, provenance tracking, structured adversarial testing of research tools, and interdisciplinary oversight. Moreover, we suggest institutional reform, including revising incentive structures, fostering AI literacy, and enforcing auditability to safeguard research integrity. In the age of machine-assisted content, credibility becomes a scarce resource. Dental science must not merely adopt AI but actively govern it to ensure that its accelerated outputs remain trustworthy, equitable, and clinically meaningful.
This study aimed to investigate how periodontitis would alter bloodstream infections (BSIs) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We hypothesized that periodontitis would alter the microbiological profile of BSIs, particularly the relative prevalence of viridans group streptococci (VGS), common oral bacteria frequently implicated in BSIs in allo-HSCT recipients, and other non-VGS organisms. We further investigated whether these microbiological changes were associated with clinical outcomes and alterations in VGS-specific humoral immune responses. A retrospective cohort ( n = 489 patients, 2010–2020) and a prospective cohort ( n = 149 patients, 2021–2022) were included for this observational study recruited from Princess Margaret Cancer Centre. Patients were categorized based on pretransplant history of periodontitis. BSIs occurring during the hospitalization period and mortality up to 1,000 days posttransplant were compared between patients with and without periodontitis. Pretransplant serum samples from the prospective cohort were analyzed for VGS-specific IgG and IgA using flow cytometry. There was no difference in the rates of BSI between groups; however, in the retrospective cohort, patients with a history of periodontitis had a higher incidence of non-VGS BSIs (76.7% vs. 56.8%, P = 0.019). A similar, though nonsignificant, trend was observed in the prospective cohort (63.4% vs. 45.8%, P = 0.16). Notably, the shift toward non-VGS BSIs was stage-dependent, increasing with advanced periodontitis in both cohorts ( P = 0.009 and P = 0.025, respectively). Patients with periodontitis had almost double the risk of mortality compared to those without (retrospective: hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.31-2.69; P < 0.001; prospective: HR = 1.82; 95% CI = 0.98-3.57; P = 0.06). Elevated VGS-specific IgG and IgA levels were observed in patients with periodontitis, with lower IgG levels correlating with VGS BSIs. History of periodontitis was associated with differences in BSI microbiology, including a higher proportion of non-VGS BSIs among patients who developed BSIs, and with poorer survival outcomes in allo-HSCT recipients.
