Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
Project description:Host-microbiome-dietary interactions play crucial roles in regulating human health, yet direct functional assessment of their interplays, cross-regulations and downstream disease impacts remains challenging. We adopted metagenome-informed metaproteomics (MIM), in both mice and humans, to simultaneously explore host, dietary, and species-level microbiome interactions across diverse scenarios, including commensal and pathogen colonization, nutritional modifications, and antibiotic-induced perturbations. Implementation of MIM in murine auto-inflammation and in human IBD characterized a ‘compositional dysbiosis’ and a concomitant, species-specific ‘functional dysbiosis’ driven by suppressed commensal responses to inflammatory host signals. Microbiome transfers unraveled early-onset kinetics of these host-commensal cross-responsive patterns, while predictive analyses identified candidate fecal host-microbiome IBD biomarker protein pairs outperforming S100A8/S100A9 (calprotectin). Importantly, a simultaneous fecal nutrient assessment enabled determination of IBD-related consumption patterns, dietary treatment compliance and small-intestinal digestive aberrations. Collectively, a parallelized dietary-bacterial-host MIM assessment functionally uncovers trans-kingdom interactomes shaping gastrointestinal ecology, while offering personalized diagnostic and therapeutic insights into microbiome-associated disease.
