Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome.

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.

Dietary Advanced Glycation End Products Have Sex- and Age-Dependent Effects on Vertebral Bone Microstructure and Mechanical Function in Mice.

Back pain is a leading cause of global disability that can arise from vertebral fracture and osteoporosis. Although poor general health and obesity are among the strongest risk factors for back pain, there is remarkably little known about how diet influences spinal diseases. Advanced glycation end-products (AGEs) are implicated in increased fracture risk, yet no studies investigated how dietary AGEs affect spinal health. We tested the hypothesis that high dietary AGE ingestion will diminish vertebral structure and function in a sex- and age-dependent manner. Female and male mice were fed low-AGE (L-AGE) or high-AGE (H-AGE) isocaloric diets for 6 and 18 months and multiple measurements of bone structure and function were taken. AGE levels in serum and cortical vertebrae were increased only for 6-month-old H-AGE female mice while blood glucose and body weight remained normal for all animals. When fed an H-AGE diet, 6-month-old female mice had inferior vertebral trabecular structure with decreased bone mineral density (BMD) and bone volume fraction. Biomechanical testing and analytical modeling further showed functional deterioration in 6-month-old H-AGE females with reduced shear and compression moduli, and maximum load to failure. At 18 months, H-AGE mice of both sexes had significant but small decreases in cortical BMD and thickness, yet functional biomechanical behaviors were not distinguishable from other aging changes. We conclude that an H-AGE diet, without diabetic or overweight conditions, diminished vertebral microstructure, mechanical behaviors, and fracture resistance in young female mice in a manner suggesting accelerated bone aging. © 2017 American Society for Bone and Mineral Research.