Project description:The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
Project description:Human breast milk (BM) plays a critical role in infant development and health, particularly in cognitive, immune, and cardiometabolic functions. BM contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs). However, to date, most studies on BMEVs have been limited in sample size. We aimed to investigate BMEV-miRNA profiles in a human population cohort, characterize BMEV-miRNAs patterns, and assess potential pathways and ontology. We thus conducted the first study to describe the EV miRNA profile of BM in 364 mothers from a population-based mother-infant cohort in the Faroe Islands using small RNA sequencing. We detected 1,523 miRNAs with ≥ one read in 70% of samples, and 447 miRNAs with ≥ one read in 100% of samples. Using hierarchical clustering, we determined five BMEV-miRNA clusters, the top three consisting of 15, 27 and 67 miRNAs. Correlation coefficients indicated that the expression of many miRNAs within the top three clusters was highly correlated. Top-cluster BMEV-miRNAs were involved in pathways enriched for the endocrine system, cellular community, neurodevelopment, and cancers. Future studies investigating determinants of BMEV-miRNAs and associated health outcomes are needed to elucidate the role of BMEV-miRNAs in health and disease.
Project description:<p>Infancy is a critical period for the colonization of the gut microbiome. However, xenobiotic effects on gut microbiome development in early life remain poorly understood. Here, we recruit 146 mother-infant pairs and collect stool samples at 3, 6, and 12 months after delivery for amplicon sequencing (N = 353), metagenomics (N = 65), and metabolomics (N = 198). Trace elements in maternal hair samples (N = 119) affect the alpha diversity of the infant gut microbiome. Shannon diversity in 3-month-old infants is correlated positively with selenium and negatively with copper, and the relative abundance of Bifidobacterium increases under high exposure to aluminum and manganese. During the first year of life, infants and their paired mothers have distinct microbial diversity and composition, and their bacterial community structures gradually approach. There are 56 differential metabolites between the first and second postpartum visits and 515 differential metabolites between the second and third visits. The typical profile of antibiotic resistance genes (ARGs) differs significantly between infants and their mothers. High copper and arsenic exposure may induce the enrichment of ARGs in the infant gut. Our findings highlight the dynamics of the gut microbiome, metabolites, and ARG profiles of mother-infant pairs after delivery, associated with prenatal exposure to trace elements.</p>