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: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.
Project description:<p>Microorganisms secrete extracellular vesicles (EVs) that transport bioactive molecules such as proteins, metabolites, and enzymes. While their functions are well studied in model microbes, their ecological contributions to natural ecosystems remain largely unexplored.To address this issue, we performed a year-long, integrative study investigating the role of environmental EVs in shaping microbial community assembly in the Xinglinwan Reservoir (XLR). By combining shotgun metagenomics, genome-scale metabolic modelling, and multi-omics of field EVs, we found that EVs mediated metabolite exchanges mainly through carrying signal molecules, amino acids, disaccharides, and CAZymes. These cargoes could be derived from the metabolisms within EVs or directly sourced from their donors, and were closely linked to the carbon cycle and nitrogen metabolism in aquatic environments. In addition, EVs increased the contribution of stochastic processes to the community assembly and improved the stability of the community by maintaining high functional redundancy. Our study demonstrates that EV-mediated metabolic exchanges are prevalent in aquatic communities and pivotal for shaping community assembly and driving biogeochemical cycles. These results clarify the ecological functions of EVs in natural habitats and provide new insights into manipulating microbial communities through controlling environmental EVs.</p>