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The oral microbiota plays an important role in the exogenous nitrate reduction pathway and is associated with heart and periodontal disease and cigarette smoking. We describe smoking-related changes in oral microbiota composition and resulting potential metabolic pathway changes that may explain smoking-related changes in disease risk. We analyzed health information and salivary microbiota composition among 1601 Cooperative Health Research in South Tyrol participants collected 2017–2018. Salivary microbiota taxa were assigned from amplicon sequences of the 16S-V4 rRNA and used to describe microbiota composition and predict metabolic pathways. Aerobic taxa relative abundance decreased with daily smoking intensity and increased with years since cessation, as did inferred nitrate reduction. Former smokers tended to be more similar to Never smokers than to Current smokers, especially those who had quit for longer than 5 years. Cigarette smoking has a consistent, generalizable association on oral microbiota composition and predicted metabolic pathways, some of which associate in a dose-dependent fashion. Smokers who quit for longer than 5 years tend to have salivary microbiota profiles comparable to never smokers.

Purpose of ReviewWe describe different methods for microbiome assessment and analysis and highlight some of the challenges of using omics data in epidemiologic studies of adverse pregnancy outcomes.Recent FindingsHuman microbiomes are dynamic and vary by ancestry and geography. The composition and dynamics of the vaginal microbiome have been associated with risk of preterm birth.SummaryThere are several different methods for characterizing the microbiome. Choice of method depends on the research question and resources available. Added to known challenges of conducting and analyzing epidemiologic studies are the unique challenges associated with microbiome detection and analysis. The resulting omics assessments of human microbial communities have great potential to identify prognostics, diagnostics, and potentially therapeutics for adverse pregnancy outcomes.

Background Early childhood caries (ECC)—dental caries (cavities) occurring in primary teeth up to age 6 years—is a prevalent childhood oral disease with a microbial etiology. Streptococcus mutans was previously considered a primary cause, but recent research promotes the ecologic hypothesis, in which a dysbiosis in the oral microbial community leads to caries. In this incident, density sampled case-control study of 189 children followed from 2 months to 5 years, we use the salivary bacteriome to (1) prospectively test the ecological hypothesis of ECC in salivary bacteriome communities and (2) identify co-occurring salivary bacterial communities predicting future ECC. Results Supervised classification of future ECC case status using salivary samples from age 12 months using bacteriome-wide data (AUC-ROC 0.78 95% CI (0.71–0.85)) predicts future ECC status before S. mutans can be detected. Dirichlet multinomial community state typing and co-occurrence network analysis identified similar robust and replicable groups of co-occurring taxa. Mean relative abundance of a Haemophilus parainfluenzae/Neisseria/Fusobacterium periodonticum group was lower in future ECC cases (0.14) than controls (0.23, P value < 0.001) in pre-incident visits, positively correlated with saliva pH (Pearson rho = 0.33, P value < 0.001) and reduced in individuals who had acquired S. mutans by the next study visit (0.13) versus those who did not (0.20, P value < 0.01). In a subset of whole genome shotgun sequenced samples ( n = 30), case plaque had higher abundances of antibiotic production and resistance gene orthologs, including a major facilitator superfamily multidrug resistance transporter (MFS DHA2 family P BH value = 1.9 × 10 −28 ), lantibiotic transport system permease protein ( P BH value = 6.0 × 10 −6 ) and bacitracin synthase I ( P BH value = 5.6 × 10 −6 ). The oxidative phosphorylation KEGG pathway was enriched in case plaque ( P BH value = 1.2 × 10 −8 ), while the ABC transporter pathway was depleted ( P BH value = 3.6 × 10 −3 ). Conclusions Early-life bacterial interactions predisposed children to ECC, supporting a time-dependent interpretation of the ecological hypothesis. Bacterial communities which assemble before 12 months of age can promote or inhibit an ecological succession to S. mutans dominance and cariogenesis. Intragenera competitions and intergenera cooperation between oral taxa may shape the emergence of these communities, providing points for preventive interventions. Eccg-4PVrgNpSeqtbeooYw Video Abstract

Background Exposure to systemic racism is linked to increased dementia burden. To assess systemic inflammation as a potential pathway linking exposure to racism and dementia disparities, we investigated the mediating role of C-reactive protein (CRP), a systemic inflammation marker, and the moderating role of the racialization process in incident dementia. Methods In the US Health and Retirement Study (n = 6,908), serum CRP was measured at baseline (2006, 2008 waves). Incident dementia was classified by cognitive tests over a six-year follow-up. Self-reported racialized categories were a proxy for exposure to the racialization process. We decomposed racialized disparities in dementia incidence (non-Hispanic Black and/or Hispanic vs. non-Hispanic white) into 1) the mediated effect of CRP, 2) the moderated portion attributable to the interaction between racialized group membership and CRP, and 3) the controlled direct effect (other pathways through which racism operates). Results The 6-year cumulative incidence of dementia is 12%. Among minoritized participants (i.e., non-Hispanic Black and/or Hispanic), high CRP levels ( ≥ 75 th percentile or 4.73μg/mL) are associated with 1.26 (95%CI: 0.98, 1.62) times greater risk of incident dementia than low CRP ( < 4.73μg/mL). Decomposition analysis comparing minoritized versus non-Hispanic white participants shows that the mediating effect of CRP accounts for 3% (95% CI: 0%, 6%) of the racial disparity, while the interaction effect between minoritized group status and high CRP accounts for 14% (95% CI: 1%, 27%) of the disparity. Findings are robust to potential violations of causal mediation assumptions. Conclusions Minoritized group membership modifies the relationship between systemic inflammation and incident dementia. Plain language summary Higher levels of inflammation in blood are linked to greater dementia risk in older adults. Non-Hispanic Black and Hispanic Americans have higher inflammation levels compared to non-Hispanic white Americans. We conducted a study to examine whether high levels of inflammation could explain differences in dementia risk among these racial groups. We found that differences in inflammation levels in non-Hispanic Black or Hispanic adults modestly explain their higher risk of dementia compared to non-Hispanic white adults. These findings suggest that interventions aimed at reducing high levels of inflammation in minoritized US adults could ameliorate racial differences in dementia risk. Higgins Tejera et al. employ mediation-interaction decomposition analyses in a large population study to demonstrate how the racialization process and systemic inflammation interact to explain racial disparities in dementia risk. They propose a causal framework to integrate biological pathways in the study of racial disparities in health.

Objective: The interactions between yeast and streptococci species that lead to dental decay and gingivitis are poorly understood. Our study describes these associations among a cohort of 101 post-partum women enrolled in the Center for Oral Health Research in Appalachia, 2012-2013. Methods: All eligible women without dental caries were included (n = 21) and the remainder were randomly sampled to represent the total number of decayed, missing, and filled teeth (DMFT) at enrollment. We used amplicon sequencing and qPCR of saliva from 2, 6, 12 and 24 visits to determine microbiome composition. Results: Active decay and generalized gingivitis were strongly predictive of each other. Using adjusted marginal models, Candida albicans and Streptococcus mutans combined were associated with active decay (OR = 3.13; 95% CI 1.26, 7.75). However, C. albicans alone (OR = 2.33; 95% CI: 0.81, 6.75) was associated with generalized gingivitis, but S. mutans alone was not (OR = 0.55; 95% CI: 0.21, 1.44). Models including microbiome community state types (CSTs) showed CSTs positively associated with active decay were negatively associated with generalized gingivitis. Discussion: C. albicans is associated with active decay and generalized gingivitis, but whether one or both are present depends on the structure of the co-existing microbial community.

The prenatal environment influences lifetime health; epigenetic mechanisms likely predominate. In 2016, the first international consortium paper on cigarette smoking during pregnancy and offspring DNA methylation identified extensive, reproducible exposure signals. This finding raised expectations for epigenome-wide association studies (EWAS) of other exposures. We review the current state-of-the-science for DNA methylation associations across prenatal exposures in humans and provide future recommendations. We reviewed 134 prenatal environmental EWAS of DNA methylation in newborns, focusing on 51 epidemiological studies with meta-analysis or replication testing. Exposures spanned cigarette smoking, alcohol consumption, air pollution, dietary factors, psychosocial stress, metals, other chemicals, and other exogenous factors. Of the reproducible DNA methylation signatures, we examined implementation as exposure biomarkers. Only 19 (14%) of these prenatal EWAS were conducted in cohorts of 1,000 or more individuals, reflecting the still early stage of the field. To date, the largest perinatal EWAS sample size was 6,685 participants. For comparison, the most recent genome-wide association study for birth weight included more than 300,000 individuals. Replication, at some level, was successful with exposures to cigarette smoking, folate, dietary glycemic index, particulate matter with aerodynamic diameter and , nitrogen dioxide, mercury, cadmium, arsenic, electronic waste, PFAS, and DDT. Reproducible effects of a more limited set of prenatal exposures (smoking, folate) enabled robust methylation biomarker creation. Current evidence demonstrates the scientific premise for reproducible DNA methylation exposure signatures. Better powered EWAS could identify signatures across many exposures and enable comprehensive biomarker development. Whether methylation biomarkers of exposures themselves cause health effects remains unclear. We expect that larger EWAS with enhanced coverage of epigenome and exposome, along with improved single-cell technologies and evolving methods for integrative multi-omics analyses and causal inference, will expand mechanistic understanding of causal links between environmental exposures, the epigenome, and health outcomes throughout the life course. https://doi.org/10.1289/EHP12956.

INTRODUCTION Neuropsychiatric symptoms in dementia (NPS) collectively refer to behavioral and psychological symptoms affecting individuals with mild cognitive impairment (MCI) or Alzheimer's disease or related dementia (ADRD). NPS are among the most troubling aspects of living with dementia but their treatments have limited efficacy. We aim to investigate genetic variants contributing to NPS to identify new therapeutic targets. METHODS We performed a genome‐wide association study (GWAS) for nine NPS domains measured by the Neuropsychiatric Symptom Inventory Questionnaire (NPI‐Q) in 12,800 participants from Alzheimer's Disease Research Centers across the United States. We performed a replication analysis in two independent cohorts. RESULTS We found genome‐wide significant signals for agitation, anxiety, apathy, delusions, and hallucinations that were driven by the apolipoprotein E (APOE) ε4 allele. We replicated these findings in ADNI and BioVU cohorts. Mediation analyses revealed that, except for apathy, MCI/ADRD severity only partially mediated the GWAS signals. DISCUSSION These findings suggest the APOE ε4 allele influences several NPS independently of and beyond its effect on ADRD. Highlights Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment and dementia. Effective NPS treatments are pressingly needed, and genetic studies can inform treatment targets to develop effective therapeutics. We conducted a genome‐wide association study of NPS in over 12,800 individuals and a replication analysis in two independent cohorts. We found apolipoprotein E (APOE) single‐nucleotide polymorphisms (SNPs) associated with multiple NPS domains beyond their effects on cognitive impairment.

Background The research on binge eating has overwhelmingly focused on Whites. We aimed to study gender and ethnic differences in the association between body image dissatisfaction and binge eating in a nationally representative sample of Black adults in the USA. Methods This cross-sectional study used data from the National Survey of American Life (NSAL), 2003–2004. Self-identified Caribbean Black ( n  = 1621) and African American (3570) adults aged 18 and older were enrolled. The independent variable was body dissatisfaction measured with two items. Using the World Health Organization Composite International Diagnostic Interview (WHO-CIDI), outcome was lifetime binge eating without hierarchy according to the DSM-IV criteria. Covariates included age, socioeconomic factors (i.e., education and marital status), and body mass index. Ethnicity and gender were focal moderators. Logistic regressions were used for data analysis. Results Despite comparable prevalence of lifetime binge eating (5 vs 4 %, p  > 0.05), African Americans reported higher body image dissatisfaction than Caribbean Blacks (36 vs 29 %, p  > 0.05). In the pooled sample, body dissatisfaction was a strong predictor of lifetime binge eating disorders. There was a significant interaction ( p  = 0.039) between ethnicity and body image dissatisfaction on binge eating, suggesting a stronger association between body image dissatisfaction and lifetime binge eating for Caribbean Blacks (OR = 11.65, 95 % 6.89–19.72) than African Americans (OR = 6.72, 95 % CI 3.97–11.37). Gender did not interact with body image dissatisfaction on binge eating. Conclusion Ethnic variation in the link between body image dissatisfaction and binge eating may be due to within-race cultural differences in body image between African Americans and Caribbean Blacks. This may include different definitions, norms, and expectations regarding the body size. Findings suggest that ethnicity may bias relevance of body image dissatisfaction as a diagnostic criterion for binge eating disorders among diverse populations of Blacks.

The impact of the oral microbiome on head and neck cancer pathogenesis and outcomes requires further study. 16s rRNA was isolated and amplified from pre-treatment oral wash samples for 52 cases and 102 controls. The sequences were binned into operational taxonomic units (OTUs) at the genus level. Diversity metrics and significant associations between OTUs and case status were assessed. The samples were binned into community types using Dirichlet multinomial models, and survival outcomes were assessed by community type. Twelve OTUs from the phyla Firmicutes, Proteobacteria, and Acinetobacter were found to differ significantly between the cases and the controls. Beta-diversity was significantly higher between the cases than between the controls (p < 0.01). Two community types were identified based on the predominant sets of OTUs within our study population. The community type with a higher abundance of periodontitis-associated bacteria was more likely to be present in the cases (p < 0.01), in older patients (p < 0.01), and in smokers (p < 0.01). Significant differences between the cases and the controls in community type, beta-diversity, and OTUs indicate that the oral microbiome may play a role in HNSCC.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.