Genome-wide analysis of whole-lung and alveolar macrophages before and after gut microbiome depletion
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE53174 | GEO | 2016/12/09
SECONDARY ACCESSION(S): PRJNA231772
REPOSITORIES: GEO
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Project description:Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline. Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome. Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.
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Project description:To study the effect of alterations in microbial density on the host, conventional C57Bl6 mice were treated with polymyxin B, ciprofloxacin, vancomycin, clindamycin, or ampicillin for 4 weeks. These antibiotic regimens result in a differential reduction in fecal microbial density. RNA-seq of whole tissue from the proximal colon was performed on the antibiotic treated mice, germ free controls, and non-antibiotic treated controls to interrogate transcriptional changes in the host.
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Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects
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Project description:Erythromycin (ERY) is a commonly used antibiotic that can be found in wastewater effluents globally. Due to the mechanisms by which they kill and prevent bacterial growth, antibiotics can have significant unwanted impacts on the fish gut microbiome. The overall objective of this project was to assess the effects of erythromycin and an antibiotic mixture on fish gut microbiomes. The project was split into two experiments to assess gut microbiome in response to exposure with ERY alone or in mixture with other common antibiotics. The objectives of experiment 1 were to understand uptake and depuration of ERY in juvenile rainbow trout (RBT) over a 7 d uptake followed by a 7 d depuration period using three concentrations of ERY. Furthermore, throughout the study changes in gut microbiome response were assessed. In experiment 2, a follow-up study was conducted using an identical experimental design to assess the impacts of an antibiotic-mixture (ERY, ampicillin, metronidazole, and ciprofloxacin at 100 µg/g each). Here, three matrices were analyzed, with gut collected for 16s metabarcoding, plasma for untargeted metabolomics, and brain for mRNA-seq analysis. ERY was depurated from the fish relatively quickly and gut microbiome dysbiosis was observed at 7 d after exposure, with a slight recovery after the 7 d depuration period. A greater number of plasma metabolites was dysregulated at 14 d compared to 7 d revealing temporality compared to gut microbiome dysbiosis. Furthermore, several transformation products of antibiotics and biomarker metabolites were observed in plasma due to antibiotic exposure. Brain transcriptome revealed only slight alterations due to antibiotic exposure. The results of these studies will help inform aquaculture practitioners and risk assessors when assessing the potential impacts of antibiotics in fish feed and the environment, with implications for host health.
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Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.
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