The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes ‘omics’ data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.

The microbiome of the female reproductive tract has implications for women’s reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.

Background and Aims: Bile acids are hepatic metabolites and have many properties considered to be relevant to the pathophysiology of NAFLD. Circulating levels of the intestinal microbiome‐modified bile acid deoxycholate are increased in cirrhosis. Approach and Results: To further elucidate the role of bile acids and intestinal microbiota linked to bile acids in progressively severe NAFLD, a multiomic study of feces including 16S rRNA sequencing, microbial transcriptomics and metabolomics was performed in a cohort with varying phenotypes of NAFLD. Several bile acids of microbial origin derived from deoxycholic acid (DCA) (glycodeoxycholate, 7‐ketodeoxycholic acid, dehydrocholic acid) increased with disease activity and fibrosis stage. These were linked to increased expression of microbial bile salt hydrolase, bile acid operon (BaiCD) and hydroxysteroid dehydrogenases (hdhA) required for DCA and downstream metabolite synthesis providing a mechanistic basis for altered bile acid profiles with disease progression. Bacteroidetes and several genera of Lachnospiraceae family containing DCA generating genes increased with increasing disease severity, whereas several potentially beneficial microbes sensitive to antibacterial effects of DCA e.g., Ruminococcaceae were decreased. The clinical relevance of these data was confirmed in an independent cohort enrolled in a clinical trial for NASH where at entry DCA and its conjugates were associated with advanced fibrosis. In patients treated with placebo, DCA declined in those with fibrosis regression and increased in those with fibrosis progression. DCA rose further in those with compensated cirrhosis when they experienced decompensation. Conclusions: These findings demonstrate a role for bile acids and the bile acid dependent microbiome in the development and progression of NAFLD and set the stage to leverage these findings for NASH biomarker development and for therapeutics.

Background: Declining physical activity (PA) is a hallmark of aging. Wearable technology provides reliable measures of the frequency, duration, intensity, and timing of PA. Accelerometry-derived measures of PA are compared with established predictors of 5-year all-cause mortality in older adults in terms of individual, relative, and combined predictive performance.Methods: Participants aged between 50 and 85 years from the 2003–2006 National Health and Nutritional Examination Survey (NHANES, n = 2,978) wore a hip-worn accelerometer in the free-living environment for up to 7 days. A total of 33 predictors of 5-year all-cause mortality (number of events = 297), including 20 measures of objective PA, were compared using univariate and multivariate logistic regression.Results: In univariate logistic regression, the total activity count was the best predictor of 5-year mortality (Area under the Curve (AUC) = 0.771) followed by age (AUC = 0.758). Overall, 9 of the top 10 predictors were objective PA measures (AUC from 0.771 to 0.692). In multivariate regression, the 10-fold cross-validated AUC was 0.798 for the model without objective PA variables (9 predictors) and 0.838 for the forward selection model with objective PA variables (13 predictors). The Net Reclassification Index was substantially improved by adding objective PA variables (p < .001).Conclusions: Objective accelerometry-derived PA measures outperform traditional predictors of 5-year mortality, including age. This highlights the importance of wearable technology for providing reproducible, unbiased, and prognostic biomarkers of health.

Integrated multiomics network analysis reveals signaling profiles in lung cancer.