Although the prominent role of the microbiome in human health has been established, the early-life microbiome is now being recognized as a major influence on long-term human health and development. Variations in the composition and functional potential of the early-life microbiome are the result of lifestyle factors, such as mode of birth, breastfeeding, diet, and antibiotic usage. In addition, variations in the composition of the early-life microbiome have been associated with specific disease outcomes, such as asthma, obesity, and neurodevelopmental disorders. This points toward this bacterial consortium as a mediator between early lifestyle factors and health and disease. In addition, variations in the microbial intrauterine environment may predispose neonates to specific health outcomes later in life. A role of the microbiome in the Developmental Origins of Health and Disease is supported in this collective research. Highlighting the early-life critical window of susceptibility associated with microbiome development, we discuss infant microbial colonization, beginning with the maternal-to-fetal exchange of microbes in utero and up through the influence of breastfeeding in the first year of life. In addition, we review the available disease-specific evidence pointing toward the microbiome as a mechanistic mediator in the Developmental Origins of Health and Disease.

The long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman’s life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention. Despite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland’s structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals—including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols—and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers. An integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective.

The human microbiota is a key contributor to many aspects of human health and its composition is largely influenced by diet. There is a growing body of scientific evidence to suggest that gut dysbiosis (microbial imbalance of the intestine) is associated with inflammatory and immune-mediated diseases (e.g., inflammatory bowel disease and asthma). Regular consumption of fermented foods (e.g., kimchi, kefir, etc.) may represent a potential avenue to counter the proinflammatory effects of gut dysbiosis. However, an assessment of the available literature in this research area is lacking. Here we provide a critical review of current human intervention studies that analyzed the effect of fermented foods on the composition and/or function of the human gut microbiota. A total of 19 human intervention studies were identified that met this search criteria. In this review, we discuss evidence that consumption of fermented foods may modify the gut microbiota in humans. Further, there is cursory evidence to suggest that gut microbiota compositional changes mediate associations between fermented food consumption and human health outcomes. Although promising, there remains considerable heterogeneity in the human populations targeted in the intervention studies we identified. Larger longitudinal feeding studies with longer follow-up are necessary to confirm and enhance the current data. Further, future studies should consider analyzing microbiota function as a means to elucidate the mechanism linking fermented food consumption with human health. This review highlights methodologic considerations for intervention trials, emphasizing an expanse of research opportunities related to fermented food consumption in humans.

Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4). Total breast volume, absolute fibro-glandular volume (FGV), and %FGV were evaluated at B4 using dual X-ray absorptiometry. The impact of AgeAccel (mean: 0; SD: 3.78) across puberty on the time to breast development (thelarche), menarche, and pubertal tempo (thelarche to menarche) was estimated using accelerated failure time models; generalized estimating equations were used to evaluate associations with breast density. A five-year increase in average adolescent AgeAccel was associated with a significant decrease in time to menarche [hazard ratio (HR): 1.37; 95% confidence interval (CI): 1.04, 1.80] adjusting for birth weight, maternal pre-pregnancy body mass index, maternal height, maternal education, B2 height, fat percentage, and cell composition. AgeAccel displayed a stronger inverse association with pubertal tempo (HR: 1.48; 95% CI: 1.10, 1.99). A five-year increase in AgeAccel was associated with 5% greater %FGV, adjusting for B4 percent body fat, and maternal traits (95% CI: 1.01, 1.10). Our study provides unique insight into the influence of AgeAccel on pubertal development in girls, which may have implications for adult health.

The age of menarche has been associated with metabolic and cardiovascular disease, as well as cancer risk. The decline in menarcheal age over the past century may be partially attributable to increased exposure to endocrine disrupting chemicals (EDCs). We assessed the influence of 26 phenol and phthalate biomarkers on the timing of menarche in a longitudinal cohort of Chilean girls. These EDCs were quantified in urine collected prior to the onset of breast development (Tanner 1; B1), and during adolescence (Tanner 4; B4). Multivariable accelerated failure time (AFT) models were used to analyze associations between biomarker concentrations and the age of menarche adjusting for body mass index (BMI) Z-score and maternal education, accounting for within-subject correlation. Several biomarkers were significantly associated with the age at menarche; however, these associations were dependent on the timing of biomarker assessment. A log(ng/ml) increase in B1 concentrations of di(2-ethylhexyl) phthalate biomarkers was associated with later menarche (hazard ratio (HR): 0.77; 95% CI: 0.60, 0.98), whereas higher B1 concentrations of 2,5-dichlorophenol and benzophenone-3 were associated with earlier menarche (HR: 1.13; 95% CI: 1.01, 1.27; HR: 1.17; 95% CI: 1.06, 1.29, respectively). Elevated B4 concentrations of monomethyl phthalate were similarly associated with earlier menarche (HR: 1.30; 95% CI: 1.10, 1.53). The impact of monoethyl phthalate and triclosan concentrations on pubertal timing were significantly modified by BMI Z-score. Higher monoethyl phthalate and triclosan concentrations were associated with earlier menarche among overweight or obese girls, but not among those that were normal weight. This study identifies modulation of sexual maturation by specific EDC biomarkers in Latina girls.

The present study introduces the assessment of depression and depressive symptoms in the German National Cohort (NAKO), a population-based mega cohort. Distribution of core measures, and associatio...