Ontology highlight
ABSTRACT:
PROVIDER: PRJNA634887 | ENA |
REPOSITORIES: ENA
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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.
2012-10-30 | E-GEOD-38151 | biostudies-arrayexpress
Project description:Squalene makes up 12 % of human skin surface lipids, however little is known about its affects on the host skin microbiome. Here we tested the effect of squalene on genetic regulation of staphylococci, showing that it profoundly affects expression virulence or colonisation determinants, and of iron uptake systems.
2018-06-30 | E-MTAB-6352 | biostudies-arrayexpress
Project description:Abstract: Natural communities of microbes inhabiting amphibian skin, the skin microbiome, are critical to supporting amphibian health and disease resistance. To enable the pro-active health assessment and management of amphibians on Army installations and beyond, we investigated the effects of acute (96h) munitions exposures to Rana pipiens (leopard frog) tadpoles and the associated skin microbiome, integrated with RNAseq-based transcriptomic responses in the tadpole host. Tadpoles were exposed to the legacy munition 2,4,6-trinitrotoluene (TNT), the new insensitive munition (IM) formulation, IMX-101, and the IM constituents nitroguinidine (NQ) and 1-methyl-3-nitroguanidine (MeNQ). The 96h LC50 values and 95% confidence intervals were 2.6 (2.4, 2.8) for ΣTNT and 68.2 (62.9, 73.9) for IMX-101, respectively. The NQ and MeNQ exposures caused no significant impacts on survival in 96h exposures even at maximum exposure levels of 3,560 and 5,285 mg/L, respectively. However, NQ and MeNQ, as well as TNT and IMX-101 exposures, all elicited changes in the tadpole skin microbiome profile, as evidenced by significantly increased relative proportions of the Proteobacteria with increasing exposure concentrations, and significantly decreased alpha-diversity in the NQ exposure. The potential for direct and indirect effects of munitions exposures on the skin microbiome were observed. A direct effect of munitions on microbial flora included the observation of increased relative abundance of the munitions-tolerant, Aeromonadaceae and Pseudomonadaceae, in the NQ exposure. Potential indirect effects on the tadpole skin microbiome resulting from tadpole-host responses to munitions included transcriptional responses indicative of potential changes in skin mucus-layer properties as well as altered production of antimicrobial peptides and innate immune factors. Additional insights into the tadpole host’s transcriptional response to munitions exposures indicated that TNT and IMX-101 exposures each elicited significant enrichment of pathways involved in type-I and type-II xenobiotic metabolism mechanisms where dose-responsive increases in expression were observed. Significant enrichment and increased transcriptional expression of heme and iron binding functions in the TNT exposures was likely connected with known mechanisms of TNT toxicity including hemolytic anemia and methemoglobinemia. The significant enrichment and dose-responsive decrease in transcriptional expression of cell cycle pathways in the IMX-101 exposures was consistent with previous observations in fish, while significant enrichment of immune-related function in response to NQ exposure indicated potential immune suppression at the highest NQ exposure concentration. Finally, the MeNQ exposures elicited significantly decreased transcriptional expression of keratin 16, type I, a gene likely involved in keratinization processes in amphibian skin. Overall, munitions showed the potential to alter tadpole skin microbiome composition and affect transcriptional profiles in the amphibian host, some indicative of potentially impacted host health and immune status, each of which suggest potential implications for munitions exposure on disease susceptibility.
2020-10-01 | GSE154924 | GEO
Project description:Leishmania braziliensis infection results in inflammation and skin injury, with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62 L. braziliensis-infected patients. We found that overall bacterial burden and microbiome configurations dominated with Staphylococcus spp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Dual RNA-seq of human lesions revealed that high lesional S. aureus transcript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcome in L. braziliensis-infected mice colonized with S. aureus, as its neutralization reduced pathology and inflammation. These results implicate the microbiome in cutaneous leishmaniasis disease outcomes in humans and suggest host-directed therapies to mitigate the inflammatory consequences.
2023-07-27 | GSE214397 | GEO