Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13983352_1.fastq.gz | Fastqsanger.gz | |||
| SRR13983352_2.fastq.gz | Fastqsanger.gz | |||
| SRR13983353_1.fastq.gz | Fastqsanger.gz | |||
| SRR13983353_2.fastq.gz | Fastqsanger.gz | |||
| SRR13983354_1.fastq.gz | Fastqsanger.gz |
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Project description:Epithelial Ovarian Cancer (EOC) is the leading cause of gynecologic cancer death. Despite many patients achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Retrospective clinical analysis of OC patients indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. We assessed whether antibiotic (ABX) therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given control or ABX containing water (metronidazole, ampicillin, vancomycin, and neomycin) before being intraperitoneally injected with murine EOC cells. Stool was collected to confirm microbiome disruption and tumors were monitored, and cisplatin therapy was administered weekly until endpoint. EOC tumor-bearing mice demonstrate accelerated tumor growth and resistance to cisplatin therapy in ABX treated compared with nonABX treatment. Stool analysis indicated most gut microbial species were disrupted by ABX treatment except for ABX resistant bacteria. To test for role of the gut microbiome, cecal microbiome transplants (CMTs) of microbiota derived from ABX or nonABX treated mice were used to recolonize the microbiome of ABX treated mice. nonABX cecal microbiome was sufficient to ameliorate the chemoresistance and survival of ABX treated mice indicative of a gut derived tumor suppressor. Mechanistically, tumors from ABX treated compared to nonABX treated mice contained a high frequency of cancer stem cells that were augmented by cisplatin. These studies indicate an intact microbiome provides a gut derived tumor suppressor and maintains chemosensitivity that is disrupted by ABX treatment.
2022-11-01 | GSE200025 | GEO
Project description:It was recently revealed that gut microbiota promote amyloid-beta (Aβ) burden in mouse models of Alzheimer’s disease (AD). However, the underlying mechanisms when using either germ-free (GF) housing conditions or treatments with antibiotics (ABX) remained unknown. In this study, we show that GF and ABX-treated 5x familial AD (5xFAD) mice developed attenuated hippocampal Aβ pathology and associated neuronal loss, and thereby delayed disease-related memory deficits. While Ab production remained unaffected in both GF and ABX-treated 5xFAD mice, we noticed in GF 5xFAD mice enhanced microglial Aβ uptake at early stages of the disease compared to ABX-treated 5xFAD mice. Furthermore, RNA-sequencing of hippocampal microglia from SPF, GF and ABX-treated 5xFAD mice revealed distinct microbiota-dependent gene expression profiles associated with phagocytosis and altered microglial activation states. Taken together, we observed that constitutive or induced microbiota modulation in 5xFAD mice differentially controls microglial Aβ clearance mechanisms preventing neurodegeneration and cognitive deficits.
2020-07-15 | GSE154428 | GEO
Project description:Background and Objectives: Antibiotic (ABx) therapy is associated with an increased risk for Crohn´s Disease but the underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy in patients. The aim of the present study was to unravel whether this rise in PA may promote colitis development via detrimental effects on the large intestinal barrier. Design: Transwell experiments were used to assess the impact of high PA in ABx-treated patients or vancomycin/metronidazole (V/M)-treated mice on the epithelial barrier. Serine protease profiling was performed using LC-MS/MS analysis. The impact of high PA on the intestinal barrier in WT/IL10-/- mice and on colitis development in IL10-/- mice was investigated using V/M+/-oral serine protease inhibitor (AEBSF) treatment. Results: The ABx-induced high PA was found to be due to significantly increased levels of pancreatic proteases and to impair the epithelial barrier. In WT mice, the rise in PA caused a transient increase in intestinal permeability but did not affect susceptibility towards DSS-induced acute colitis. In IL10-/- mice, the rise in PA caused a lasting impairment of the intestinal barrier, which was associated with inflammatory activation of the large intestinal tissue. In the long term, the lasting increase in PA upon repeated V/M treatment aggravated colitis development in IL10-/-mice. Conclusion: High PA is a frequent adverse effect of ABx therapy which is detrimental to the large intestinal barrier and may contribute to the development of chronic inflammation in genetically susceptible individuals.
2018-05-11 | PXD007914 | Pride
Project description:The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis1 in a tissue, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we find that large peritoneal macrophages (LPMs) display impaired efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated, and germ-free mice in vivo. Mechanistically, the microbiota-derived short-chain fatty acid butyrate directly boosted efferocytosis efficiency/capacity in mouse and human macrophages, and rescued ABX-induced LPM efferocytosis defects in vivo. Bulk mRNA sequencing of butyrate-treated macrophages in vitro and single cell mRNA sequencing of LPMs isolated from ABX-treated and butyrate-rescued mice revealed regulation of efferocytosis-supportive transcriptional programs. Specifically, we found that the efferocytosis receptor T-cell immunoglobulin and mucin domain containing 4 (TIM-4, Timd4) was downregulated in LPMs of ABX-treated mice but rescued by oral butyrate and TIM-4 was required for the butyrate-induced enhancement of LPM efferocytosis capacity. LPM efferocytosis was impaired beyond withdrawal of ABX and ABX-treated mice exhibited significantly worse disease in a mouse model of lupus. Our results demonstrate that homeostatic efferocytosis relies on distal metabolic signals and suggest that defective homeostatic efferocytosis may explain link between ABX use and inflammatory disease.
2024-07-16 | GSE270514 | GEO
Project description:The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis1 in a tissue, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we find that large peritoneal macrophages (LPMs) display impaired efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated, and germ-free mice in vivo. Mechanistically, the microbiota-derived short-chain fatty acid butyrate directly boosted efferocytosis efficiency/capacity in mouse and human macrophages, and rescued ABX-induced LPM efferocytosis defects in vivo. Bulk mRNA sequencing of butyrate-treated macrophages in vitro and single cell mRNA sequencing of LPMs isolated from ABX-treated and butyrate-rescued mice revealed regulation of efferocytosis-supportive transcriptional programs. Specifically, we found that the efferocytosis receptor T-cell immunoglobulin and mucin domain containing 4 (TIM-4, Timd4) was downregulated in LPMs of ABX-treated mice but rescued by oral butyrate and TIM-4 was required for the butyrate-induced enhancement of LPM efferocytosis capacity. LPM efferocytosis was impaired beyond withdrawal of ABX and ABX-treated mice exhibited significantly worse disease in a mouse model of lupus. Our results demonstrate that homeostatic efferocytosis relies on distal metabolic signals and suggest that defective homeostatic efferocytosis may explain link between ABX use and inflammatory disease.
2024-07-16 | GSE270512 | GEO
Project description:Recent evidence suggests an important role of the gut microbiome in early life on immune cell entraining. Using two independent transgenic (Tg) lines of Alzheimer’s disease, we have demonstrated that life-long antibiotic (ABX)-perturbation of the gut microbiome is associated with reduced amyloid beta (Ab) plaque pathology and microglial phenotypes in male mice. Furthermore, fecal microbiota transfer (FMT) from age-matched APPPS1-21 Tg mice into long-term ABX-treated male APPPS1-21 mice partially restored amyloidosis and microgliosis, thus establishing causality. in the current studies, we planned to investigate the transcriptome profiles in APPPS1-21 mice treated with short-term abx (PND14-21) compared with vehicle treated groups in genotype-, sex- and time -dependent manner. Most importantly, we also investigated if fecal microbiota transplants from age-matched Tg male mice into short-term abx (PND14-21)-treated male mice restores brain transcriptomes to that of obsreved in vehicle-treated male mice at 9 weeks of age.
2021-10-25 | GSE185407 | GEO
Project description:Antibiotic-treated (ABX) mice exhibit an impaired innate and adaptive antiviral immune response and substantially delayed viral clearance following exposure to systemic LCMV or mucosal influenza virus. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity. In this study, we performed gene expression profiling to compare the transcriptional signatures of macrophages isolated from mice exposed to commensal bacteria-derived signals to macrophages isolated from mice depleted of commensal bacteria. Peritoneal macrophages (CD3ε-, CD5-, CD19-, CD11b+, F4/80+) from naïve CNV or ABX mice were sorted directly into TRIzol (Invitrogen) on a BD Aria (Beckson Dickson). Test sorts were �95% pure. For microarray analysis, RNA was extracted from 3 sorted biological replicates of peritoneal macrophages from naïve CNV or ABX mice. cDNA was amplified using NuGen WT Ovation Pico kit and hybridized to Affymetrix GeneChip Mouse Gene 1.0 ST microarrays
2015-11-05 | E-GEOD-74712 | biostudies-arrayexpress
Project description:Antibiotic-treated (ABX) mice exhibit an impaired innate and adaptive antiviral immune response and substantially delayed viral clearance following exposure to systemic LCMV or mucosal influenza virus. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity. In this study, we performed gene expression profiling to compare the transcriptional signatures of macrophages isolated from mice exposed to commensal bacteria-derived signals to macrophages isolated from mice depleted of commensal bacteria.
2015-11-05 | GSE74712 | GEO
Project description:We analyzed the effects of antibiotics using a popular model of gut microbiota depletion in mice by a cocktail of antibiotics. We combined intestinal transcriptome together with metagenomic analysis of the gut microbiota to develop a new bioinformatics approach that probes the links between microbial components and host functions. We found that most antibiotic-induced alterations can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues; and the effects of remaining antibiotic-resistant microbes. While microbe depletion led to down-regulation of immunity, the two other factors primarily inhibited mitochondrial gene expression and amounts of active mitochondria, and induced cell death. By reconstructing and analyzing a transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria. This series includes gene expression in the ileum of control, antibiotics (ABx)-treated, germfree, germfree-ABx-treated and mice colonized with normal or Abx-resistant microbiota. common reference design with a pool of small intestine RNA labeled with Cy3
2015-01-26 | E-GEOD-60566 | biostudies-arrayexpress