Chronic Oral Inoculation of Porphyromonas gingivalis and Treponema denticola Induce Different Brain Pathologies in a Mouse Model of Alzheimer Disease.

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 1ß (IL-1ß) and interleukin 6 and production of amyloid-ß 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-1ß, 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-1ß 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.

Bacterial Membrane Vesicles: The Missing Link Between Bacterial Infection and Alzheimer Disease.

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.

Social inequities in early childhood caries in Australia: A population-based study on statewide public dental services data.

BACKGROUND: Social disadvantage leads to dental caries during childhood. AIM: This study investigated whether dental caries occur earlier in children from households experiencing social disadvantage than those not experiencing social disadvantage. DESIGN: The overall risk of, and relative time to, early childhood caries (ECC) according to sociodemographic characteristics in Victoria, Australia, was quantified. Records for 134 463 children in Victoria, Australia, from 2009 to 2019 were analysed. Time ratios (TR) and hazard ratios (HR) of carious lesion(s) in early childhood were estimated. RESULTS: Compared with reference groups, Indigenous children had an adjusted TR of 0.80 (95% CI: 0.78, 0.82), children from households with languages other than English had an adjusted TR of 0.83 (95% CI: 0.82, 0.84), and dependants of concession cardholders had an adjusted TR of 0.81 (95% CI: 0.80, 0.81); therefore, 20%, 17% and 19% reduced times to the first carious lesion, respectively. The estimated HRs were 1.57 (95% CI: 1.49, 1.67) for Indigenous children, 1.46 (95% CI: 1.42, 1.50) for children from households with other languages and 1.57 (CI: 1.53, 1.60) for dependants of concession cardholders. CONCLUSION: Preventive oral health interventions must be targeted early in children from households experiencing social disadvantage to avoid social inequities in ECC.

Porphyromonas gingivalis and the pathogenesis of Alzheimer's disease.

The cause of Alzheimer's disease (AD), and the pathophysiological mechanisms involved, remain major unanswered questions in medical science. Oral bacteria, especially those species associated with chronic periodontitis and particularly Porphyromonas gingivalis, are being linked causally to AD pathophysiology in a subpopulation of susceptible individuals. P. gingivalis produces large amounts of proteolytic enzymes, haem and iron capture proteins, adhesins and internalins that are secreted and attached to the cell surface and concentrated onto outer membrane vesicles (OMVs). These enzymes and adhesive proteins have been shown to cause host tissue damage and stimulate inflammatory responses. The ecological and pathophysiological roles of P. gingivalis OMVs, their ability to disperse widely throughout the host and deliver functional proteins lead to the proposal that they may be the link between a P. gingivalis focal infection in the subgingivae during periodontitis and neurodegeneration in AD. P. gingivalis OMVs can cross the blood brain barrier and may accelerate AD-specific neuropathology by increasing neuroinflammation, plaque/tangle formation and dysregulation of iron homeostasis, thereby inducing ferroptosis leading to neuronal death and neurodegeneration.

Modulation of MG-63 Osteogenic Response on Mechano-Bactericidal Micronanostructured Titanium Surfaces.

Despite recent advances in the development of orthopedic devices, implant-related failures that occur as a result of poor osseointegration and nosocomial infection are frequent. In this study, we developed a multiscale titanium (Ti) surface topography that promotes both osteogenic and mechano-bactericidal activity using a simple two-step fabrication approach. The response of MG-63 osteoblast-like cells and antibacterial activity toward Pseudomonas aeruginosa and Staphylococcus aureus bacteria was compared for two distinct micronanoarchitectures of differing surface roughness created by acid etching, using either hydrochloric acid (HCl) or sulfuric acid (H2SO4), followed by hydrothermal treatment, henceforth referred to as either MN-HCl or MN-H2SO4. The MN-HCl surfaces were characterized by an average surface microroughness (Sa) of 0.8 ± 0.1 µm covered by blade-like nanosheets of 10 ± 2.1 nm thickness, whereas the MN-H2SO4 surfaces exhibited a greater Sa value of 5.8 ± 0.6 µm, with a network of nanosheets of 20 ± 2.6 nm thickness. Both micronanostructured surfaces promoted enhanced MG-63 attachment and differentiation; however, cell proliferation was only significantly increased on MN-HCl surfaces. In addition, the MN-HCl surface exhibited increased levels of bactericidal activity, with only 0.6% of the P. aeruginosa cells and approximately 5% S. aureus cells remaining viable after 24 h when compared to control surfaces. Thus, we propose the modulation of surface roughness and architecture on the micro- and nanoscale to achieve efficient manipulation of osteogenic cell response combined with mechanical antibacterial activity. The outcomes of this study provide significant insight into the further development of advanced multifunctional orthopedic implant surfaces.

Association Between Oral Bacteria and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pre-clinical evidence implicates oral bacteria in the pathogenesis of Alzheimer's disease (AD), while clinical studies show diverse results. OBJECTIVE: To comprehensively assess the association between oral bacteria and AD with clinical evidence. METHODS: Studies investigating the association between oral bacteria and AD were identified through a systematic search of six databases PubMed, Embase, Cochrane Central Library, Scopus, ScienceDirect, and Web of Science. Methodological quality ratings of the included studies were performed. A best evidence synthesis was employed to integrate the results. When applicable, a meta-analysis was conducted using a random-effect model. RESULTS: Of the 16 studies included, ten investigated periodontal pathobionts and six were microbiome-wide association studies. Samples from the brain, serum, and oral cavity were tested. We found over a ten-fold and six-fold increased risk of AD when there were oral bacteria (OR = 10.68 95% CI: 4.48-25.43; p < 0.00001, I2 = 0%) and Porphyromonas gingivalis (OR = 6.84 95% CI: 2.70-17.31; p < 0.0001, I2 = 0%) respectively in the brain. While AD patients exhibited lower alpha diversity of oral microbiota than healthy controls, the findings of bacterial communities were inconsistent among studies. The best evidence synthesis suggested a moderate level of evidence for an overall association between oral bacteria and AD and for oral bacteria being a risk factor for AD. CONCLUSION: Current evidence moderately supports the association between oral bacteria and AD, while the association was strong when oral bacteria were detectable in the brain. Further evidence is needed to clarify the interrelationship between both individual species and bacterial communities and the development of AD.

Trends in social inequalities in early childhood caries using population-based clinical data.

OBJECTIVE: To assess the longitudinal trends in social inequalities in early childhood caries (ECC) using collected population-based data. METHODS: Clinical data on children were routinely collected from 2008 to 2019 in Victoria, Australia. ECC prevalence and severity (dmft) were quantified according to Indigenous status, culturally and linguistically diverse (CALD) status, concession cardholder status, geographic remoteness and area deprivation. The inverse probability weighting was used to quantify social inequalities in ECC. The weighted prevalence differences, and the ratio between the weighted prevalence of ECC and mean dmft and their 95% confidence interval, were then plotted. RESULTS: Absolute inequalities in ECC prevalence increased for children by 7% for CALD status and cardholder status between 2008 and 2019. Likewise, absolute inequalities in ECC severity in this time period increased by 0.6 for CALD status and by 0.4 for cardholder status. Relative inequalities in ECC increased by CALD (ratio: 1.3 to 2.0), cardholder status (1.3 to 2.0) and area deprivation (1.1 to 1.3). Relative inequalities in severity increased by CALD (1.5 to 2.8), cardholder (1.4 to 2.5) or area deprivation (1.3 to 1.5). Although children with Indigenous status experienced inequalities in ECC prevalence and severity, these did not increase on the absolute (ECC: 0.1-0.1 Severity: 1.0-0.1) or relative scale (ECC ratio: 1.3-1.3 Severity ratio: 1.6-1.1). CONCLUSIONS: Trends in inequalities in ECC were different according to sociodemographic measures. Oral health policies and interventions must be evaluated on the basis of reducing the prevalence of oral diseases and oral health inequalities between population sub-groups.

The Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics in Oral Cancer Management.

Oral carcinogenesis is preceded by oral diseases associated with inflammation such as periodontitis and oral candidiasis, which are contributed by chronic alcoholism, smoking, poor oral hygiene, and microbial infections. Dysbiosis is an imbalance of microbial composition due to oral infection, which has been reported to contribute to oral carcinogenesis. Therefore, in this review, we summarised the role of probiotics, prebiotics, synbiotics, and postbiotics in promoting a balanced oral microbiome, which may prevent oral carcinogenesis due to oral infections. Probiotics have been shown to produce biofilm, which possesses antibacterial activity against oral pathogens. Meanwhile, prebiotics can support growth and increase the benefit of probiotics. In addition, postbiotics possess antibacterial, anticariogenic, and anticancer properties that potentially aid in oral cancer prevention and treatment. The use of probiotics, prebiotics, synbiotics, and postbiotics for oral cancer management is still limited despite their vast potential, thus, discovering their prospects could herald a novel approach to disease prevention and treatment while participating in combating antimicrobial resistance.

Breastmilk influences development and composition of the oral microbiome.

Background: Human microbiomes assemble in an ordered, reproducible manner yet there is limited information about early colonisation and development of bacterial communities that constitute the oral microbiome. Aim: The aim of this study was to determine the effect of exposure to breastmilk on assembly of the infant oral microbiome during the first 20 months of life. Methods: The oral microbiomes of 39 infants, 13 who were never breastfed and 26 who were breastfed for more than 10 months, from the longitudinal VicGeneration birth cohort study, were determined at four ages. In total, 519 bacterial taxa were identified and quantified in saliva by sequencing the V4 region of the bacterial 16S rRNA genes. Results: There were significant differences in the development of the oral microbiomes of never breastfed and breastfed infants. Bacterial diversity was significantly higher in never breastfed infants at 2 months, due largely to an increased abundance of Veillonella and species from the Bacteroidetes phylum compared with breastfed infants. Conclusion: These differences likely reflect breastmilk playing a prebiotic role in selection of early-colonising, health-associated oral bacteria, such as the Streptococcus mitis group. The microbiomes of both groups became more heterogenous following the introduction of solid foods.

The Microbiome in Pancreatic Cancer-Implications for Diagnosis and Precision Bacteriophage Therapy for This Low Survival Disease.

While the mortality rates for many cancers have decreased due to improved detection and treatments, that of pancreatic cancer remains stubbornly high. The microbiome is an important factor in the progression of many cancers. Greater understanding of the microbiome in pancreatic cancer patients, as well as its manipulation, may assist in diagnosis and treatment of this disease. In this report we reviewed studies that compared microbiome changes in pancreatic cancer patients and non-cancer patients. We then identified which bacterial genera were most increased in relative abundance across the oral, pancreatic, duodenal, and faecal tissue microbiomes. In light of these findings, we discuss the potential for utilising these bacteria as diagnostic biomarkers, as well as their potential control using precision targeting with bacteriophages, in instances where a causal oncogenic link is made.

Temporal development of the infant oral microbiome.

The human oral microbiome is becoming recognized as playing roles in health and disease well beyond the oral cavity over the lifetime of the individual. The oral microbiome is hypothesized to result from specific colonization events followed by a reproducible and ordered development of complex bacterial communities. Colonization events, proliferation, succession and subsequent community development are dependent on a range of host and environmental factors, most notably the neonate diet. It is now becoming apparent that early childhood and prenatal influences can have long term effects on the development of human oral microbiomes. In this review, the temporal development of the infant human oral microbiome is examined, with the effects of prenatal and postnatal influences and the roles of specific bacteria. Dietary and environmental factors, especially breastfeeding, have a significant influence on the development of the infant oral microbiome. The evidence available regarding the roles and functions of early colonizing bacteria is still limited, and gaps in knowledge where further research is needed to elucidate these specific roles in relation to health and disease still exist.

Streptococcus salivarius K12 inhibits Candida albicans aggregation, biofilm formation and dimorphism.

Candida albicans causes candidiasis, particularly in immunocompromised patients. Streptococcus salivarius K12 (K12) is a probiotic isolated from a healthy oral cavity. The study aimed to determine the effect of K12 on C. albicans aggregation, biofilm formation and dimorphism. C. albicans ATCC MYA-4901, acquired immunodeficiency syndrome (AIDS) isolate (ALC2), and oral cancer isolate (ALC3) and K12 were used in the study. All C. albicans strains and K12 were grown in yeast peptone dextrose agar and brain heart infusion agar, respectively, prior to aggregation, biofilm and dimorphism assays. Auto-aggregation of C. albicans MYA-4901 and ALC2 was categorised as high, while the co-aggregation of the strains was low in the presence of K12. C. albicans total cell count decreased significantly when co-cultured with K12 compared with monocultured C. albicans biofilm (p < 0.05). Inhibition of yeast-to-hyphae transition was also observed when co-cultured with K12. In conclusion, K12 inhibits C. albicans aggregation, biofilm formation and dimorphism.

Isolation and Functional Characterization of Fusobacterium nucleatum Bacteriophage.

Bacteriophages are viruses that specifically lyse bacteria. They have demonstrated potential in applications as antibacterial agents in medicine, agriculture, and environmental remediation. Due to the complex and dynamic nature of the oral microbiome, antibiotic treatment of chronic, polymicrobial oral diseases may lead to dysbiosis. In these diseases, bacteriophages may provide targeted activity against oral bacteria without such disruption to the broader microbial community. In this chapter, we describe the methods for screening samples that may contain bacteriophages against oral pathogenic bacteria, and using the example of FNU1, the bacteriophage we isolated against Fusobacterium nucleatum, describe the process of bacteriophage purification and characterization.

Oral Antibiotic for Empirical Management of Acute Dentoalveolar Infections-A Systematic Review.

Concerns regarding increasing antibiotic resistance raise the question of the most appropriate oral antibiotic for empirical therapy in dentistry. The aim of this systematic review was to investigate the antibiotic choices and regimens used to manage acute dentoalveolar infections and their clinical outcomes. A systematic review was undertaken across three databases. Two authors independently screened and quality-assessed the included studies and extracted the antibiotic regimens used and the clinical outcomes. Searches identified 2994 studies, and after screening and quality assessment, 8 studies were included. In addition to incision and drainage, the antibiotics used to manage dentoalveolar infections included amoxicillin, amoxicillin/clavulanic acid, cefalexin, clindamycin, erythromycin, metronidazole, moxifloxacin, ornidazole and phenoxymethylpenicillin. Regimens varied in dose, frequency and duration. The vast majority of regimens showed clinical success. One study showed that patients who did not receive any antibiotics had the same clinical outcomes as patients who received broad-spectrum antibiotics. The ideal choice, regimen and spectrum of empirical oral antibiotics as adjunctive management of acute dentoalveolar infections are unclear. Given that all regimens showed clinical success, broad-spectrum antibiotics as first-line empirical therapy are unnecessary. Narrow-spectrum agents appear to be as effective in an otherwise healthy individual. This review highlights the effectiveness of dental treatment to address the source of infection as being the primary factor in the successful management of dentoalveolar abscesses. Furthermore, the role of antibiotics is questioned in primary space odontogenic infections, if drainage can be established.

Bacteriophage manipulation of the microbiome associated with tumour microenvironments-can this improve cancer therapeutic response?

Some cancer treatment failures have been attributed to the tumour microbiota, with implications that microbiota manipulation may improve treatment efficacy. While antibiotics have been used to control bacterial growth, their dysbiotic effects on the microbiome, failure to penetrate biofilms and decreased efficacy due to increasing antimicrobial resistance by bacteria, suggest alternatives are needed. Bacteriophages may provide a precise means for targeting oncobacteria whose relative abundance is increased in tumour tissue microbiomes. Fusobacterium, Streptococcus, Peptostreptococcus, Prevotella, Parvimonas, and Treponema species are prevalent in tumour tissue microbiomes of some cancers. They may promote cancer growth by dampening immunity, stimulating release of proinflammatory cytokines, and directly interacting with cancer cells to stimulate proliferation. Lytic bacteriophages against some of these oncobacteria have been isolated and characterised. The search continues for others. The possibility exists for their testing as adjuncts to complement existing therapies. In this review, we highlight the role of oncobacteria, specifically those whose relative abundance in the intra-tumour microbiome is increased, and discuss the potential for bacteriophages against these micro-organisms to augment existing cancer therapies. The capacity for bacteriophages to modulate immunity and kill specific bacteria makes them suitable candidates to manipulate the tumour microbiome and negate the effects of these oncobacteria.

Bugs and Brains, the Gut and Mental Health Study: a mixed-methods study investigating microbiota composition and function in anxiety, depression and irritable bowel syndrome.

INTRODUCTION: Research has highlighted relationships between the micro-organisms that inhabit our gastrointestinal tract (oral and gut microbiota) with host mood and gastrointestinal functioning. Mental health disorders and functional gastrointestinal disorders co-occur at high rates, although the mechanisms underlying these associations remain unclear. The Bugs and Brains Study aims to investigate complex relationships between anxiety/depression and irritable bowel syndrome (IBS) in two ways. First, its primary component will compare the gut and oral microbiota in females with anxiety/depression and/or IBS relative to controls, and investigate underlying physiological, endocrine and immune factors, as well as associations with diet and psychosocial factors. In an ancillary component, the study will also investigate gastrointestinal and mental health symptoms in a larger sample, and explore relationships with diet, exercise, oral health, substance use, medical history, early life adversity and psychosocial factors. METHODS AND ANALYSIS: The Bugs and Brains Study aims to recruit 160 females to the primary component: (1) 40 controls; (2) 40 participants with a depressive/anxiety disorder, but no IBS; (3) 40 participants with IBS, but no depressive/anxiety disorder and (4) 40 participants with both depressive/anxiety disorder and IBS. Participation is completed within 1 month, and involves comprehensive questionnaires, anthropometrics, a diagnostic clinical interview, collection of two saliva samples, and stool, urine and hair samples. This study aims to use a systems biology approach to characterise oral and gut microbial composition and function using 16S rRNA gene sequencing and nuclear MR spectroscopy. As part of the ancillary component, it will collect questionnaire data from 1000 participants aged 18-40 years, capturing mental health, gastrointestinal health, oral health, diet and psychosocial factors. ETHICS AND DISSEMINATION: Approval was granted by the University of Melbourne Human Research Ethics Committee (#1749221). All participants voluntarily provided informed consent. Results will be published in peer-reviewed journals and presented at scientific conferences.

Nutrition and oral health in early childhood: associations with formal and informal childcare.

OBJECTIVE: To examine associations between childcare type and nutrition and oral health indicators. DESIGN: Cross-sectional data extracted from a longitudinal birth cohort. Parent-completed FFQ and questions regarding oral health and childcare use. The associations between childcare type, classified into four groups: parent care only (PCO), formal childcare only (FCO), informal childcare only (ICO) or combination of care (F&I), and nutrition and oral health indicators were examined. SETTING: Home and childcare. PARTICIPANTS: Families with children aged 3 years (n 273) and 4 years (n 249) in Victoria, Australia. RESULTS: No associations were observed between childcare type and core food/beverage consumption or oral health indicators. For discretionary beverages, compared with children receiving PCO at age 3 years, children in FCO or F&I were less likely to frequently consume fruit juice/drinks (FCO: adjusted OR (AOR) 0·41, 95 % CI 0·17, 0·96, P = 0·04; F&I: AOR 0·32, 95 % CI 0·14, 0·74, P = 0·008). At age 4 years, children receiving FCO or ICO were less likely to consume sweet beverages frequently compared with children receiving PCO: fruit juice/drink (ICO: AOR 0·42, 95 % CI 0·19, 0·94, P = 0·03; FCO: AOR 0·35, 95 % CI 0·14, 0·88, P = 0·03) and soft drink (ICO: AOR 0·23, 95 % CI 0·07, 0·74, P = 0·01; FCO: AOR 0·14, 95 % CI 0·03, 0·76, P = 0·02). CONCLUSIONS: Associations between childcare type and discretionary beverage intake were observed. Investigation into knowledge, attitudes and activities in formal and informal childcare settings is required to explore different health promotion practices that may influence nutrition and oral health.

Metabolic cooperativity between Porphyromonas gingivalis and Treponema denticola.

BACKGROUND:  Porphyromonas gingivalis and Treponema denticola are proteolytic periodontopathogens that co-localize in polymicrobial subgingival plaque biofilms, display in vitro growth symbiosis and synergistic virulence in animal models of disease. These symbioses are underpinned by a range of metabolic interactions including cooperative hydrolysis of glycine-containing peptides to produce free glycine, which T. denticola uses as a major energy and carbon source. OBJECTIVE:  To characterize the P. gingivalis gene products essential for these interactions. Methods: The P. gingivalis transcriptome exposed to cell-free T. denticola conditioned medium was determined using RNA-seq. P. gingivalis proteases potentially involved in hydrolysis of glycine-containing peptides were identified using a bioinformatics approach. RESULTS:  One hundred and thirty-twogenes displayed differential expression, with the pattern of gene expression consistent with succinate cross-feeding from T. denticola to P. gingivalis and metabolic shifts in the P. gingivalis folate-mediated one carbon superpathway. Interestingly, no P. gingivalis proteases were significantly up-regulated. Three P. gingivalis proteases were identified as candidates and inactivated to determine their role in the release of free glycine. P. gingivalis PG0753 and PG1788 but not PG1605 are involved in the hydrolysis of glycine-containing peptides, making free glycine available for T. denticola utilization. CONCLUSION:  Collectively these metabolic interactions help to partition resources and engage synergistic interactions between these two species.

Oral microbiome composition, but not diversity, is associated with adolescent anxiety and depression symptoms.

PURPOSE: Depression and anxiety are highly prevalent disorders, whose significant burden is compounded by the presence of oral disease. Mental health disorders and oral health may be associated via changes to the oral microbiome, involving increased pro-inflammatory communication and cortisol in saliva. The present study provides the first culture-independent investigation of the oral microbiome considering depression and anxiety symptoms in adolescence, a critical age where these conditions begin to emerge and co-occur. It also investigates whether inflammation and cortisol moderate these relationships. METHODS: Participants (N = 66) aged 14-18 years (69.70% female) self-reported oral health, depression and anxiety symptoms, and collected saliva samples across two days. Saliva was assayed for cortisol and C-reactive protein (CRP), and used for 16S rRNA gene sequencing to estimate the oral microbiome. Multivariate statistical analyses examined associations. RESULTS: Overall diversity of the oral microbiome did not differ between adolescents by anxiety or depression grouping (low versus high symptoms), and was not associated with symptom measures. Depression and anxiety symptoms were instead associated with differential abundance of specific bacterial taxa, including Spirochaetaceae, Actinomyces, Treponema, Fusobacterium and Leptotrichia spp. Several host mood-microbial relationships were moderated by proposed mechanisms, including salivary cortisol and CRP. CONCLUSIONS: Oral microbiome composition, but not diversity, was associated with adolescent anxiety and depression symptoms. Longitudinal studies considering these associations would improve mechanistic understanding. This research indicates that adolescence remains an essential developmental period to identify early targets for intervention.