Project description:Today, swine is regarded as promising biomedical model, however, its gastrointestinal microbiome dynamics have been less investigated than that of humans or murine models . The aim of this study was to establish a high-throughput multi-omics pipeline to investigate the healthy fecal microbiome of swine and its temporal dynamics as basis for future infection studies. To this end, a homogenization protocol based on deep-frozen feces followed by integrated sample preparation for different meta-omics analyses was developed. Subsequent data integration linked microbiome composition with function, i.e. expressed proteins and secreted metabolites.
Project description:The human gut is colonized by trillions of microorganisms that influence human health and disease through the metabolism of xenobiotics, including therapeutic drugs and antibiotics. The diversity and metabolic potential of the human gut microbiome have been extensively characterized, but it remains unclear which microorganisms are active and which perturbations can influence this activity. Here, we use flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the human gut contains distinctive subsets of active and damaged microorganisms, primarily composed of Firmicutes, which display marked temporal variation. Short-term exposure to a panel of xenobiotics resulted in significant changes in the physiology and gene expression of this active microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding novel candidate proteins for antibiotic resistance, drug metabolism, and stress response. These results demonstrate the power of moving beyond DNA-based measurements of microbial communities to better understand their physiology and metabolism. RNA-Seq analysis of the human gut microbiome during exposure to antibiotics and therapeutic drugs.
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:Aging is the predominant cause of morbidity and mortality in industrialized countries, yet the molecular mechanisms driving aging and especially the contribution by the microbiome remain unclear. We combined multi-omics with metabolic modeling to comprehensively characterize host–microbiome interactions during aging in mice. Our findings reveal a complex dependency of host metabolism on known and novel microbial interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome accompanied by reduced beneficial interactions between bacterial species. These microbial changes coincided with increased inflammaging as well as a corresponding downregulation of key host pathways, predicted by our model to be microbiome-dependent, that are crucial for maintaining intestinal barrier function, cellular replication, and homeostasis. Our results elucidate microbiome–host interactions that potentially influence host aging processes, focusing on microbial nucleotide metabolism as a pivotal factor in aging dynamics. These pathways could serve as future targets for the development of microbiome-based anti-aging therapies.
Project description:Seasonal influenza outbreaks represent a large burden for the healthcare system as well as the economy. While the role of the microbiome in the context of various diseases has been elucidated, the effects on the respiratory and gastrointestinal microbiome during influenza illness is largely unknown. Therefore, this study aimed to characterize the temporal development of the respiratory and gastrointestinal microbiome of swine using a multi-omics approach prior and during influenza infection. Swine is a suitable animal model for influenza research, as it is closely related to humans and a natural host for influenza viruses. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae families in the upper respiratory tract. To our surprise, temporal development of the respiratory microbiome was not affected. Furthermore, we observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, we found increased abundances of Prevotellaceae, while Clostridiaceae and Lachnospiraceae decreased. Furthermore, metaproteomics showed that the functional composition of the microbiome, known to be robust and stable under healthy conditions, was heavily affected by the influenza infection. Metabolome analysis proved increased amounts of short-chain fatty acids in the gastrointestinal tract, which might be involved in faster recovery. Furthermore, metaproteome data suggest a possible immune response towards flagellated Clostridia induced during the infection. Therefore, it can be assumed that the respiratory infection with IAV caused a systemic effect in the porcine host and microbiome.
Project description:<p>The Vaginal Microbiome Consortium team at Virginia Commonwealth University has conducted the Multi-Omic Microbiome Study: Pregnancy Initiative (MOMS-PI) in collaboration with the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) to better understand how microbiome and host profiles change throughout pregnancy and influence the establishment of the nascent microbiome in neonates. The team particularly focused on elucidation of the role of the microbiome and its components in the etiology of preterm birth, which occurs in over 10% of pregnancies and which is the leading cause of death in neonates. Samples from 1594 women and their neonates were collected throughout pregnancy, at delivery and postpartum. The group has generated a comprehensive dataset of multiple omics technologies. This longitudinal, large-scale effort was designed to provide a large-scale resource for the scientific community. The study also permits characterization of temporal dynamics of the microbiome in pregnancy and factors associated with preterm birth.</p>
Project description:Successful establishment and maintenance of pregnancy can be attained only through optimum conceptus-maternal cross talk. Despite significant progress in our understanding of the temporal changes in the transcriptome of the uterine endometrium, we have only a rudimentary knowledge of the genes and pathways governing growth and development of the bovine conceptus. In particular, very little information exists for the posthatchingembryo and elongating conceptus. This period of development is arguably the most important, as approximately 40% of all embryonic loss occurs between Days 8 and 17 of pregnancy in cattle. Here, we describe the global transcriptome profile of the bovine conceptus at five key stages of its pre- and peri-implantation growth (Days 7, 10, 13, 16, and 19) using state-of-the-art RNA sequencing techniques. More than 287 million reads were generated at the five stages, and more than 22?700 unique transcripts were detected. Analysis of variance followed by self-organizing maps identified differentially regulated (P < 0.05) genes organized in nine gene clusters forming a sequential transcript dynamics across these developmental stages. Of particular interest, genes in clusters 3 (n = 236) and 6 (n = 1409) were significantly up-regulated on Days 16 and 19, suggesting a role in maternal recognition and initiation of implantation. This transcriptome analysis of the bovine conceptus will provide a blueprint of the dynamic changes in gene expression occurring during maternal recognition and implantation and will complement existing knowledge of the temporal changes in the endometrial transcriptome, thus facilitating a better understanding of conceptus-maternal cross talk during the peri-implantation period of pregnancy. mRNA-seq study of bovine conceptuses at 5 stages of development (days 7, 10, 13, 16 and 19) post fertilization.
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.