Microbiome and Metabolome in Ischaemic Heart Disease
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PROVIDER: PRJEB46098 | ENA |
REPOSITORIES: ENA
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Project description:Background and aims: Gene mutations or variants leading to insufficient reactive oxygen species (ROS) production have been associated with inflammatory bowel disease (IBD). In particular, 40-50% of patients with chronic granulomatous disease have IBD (CGD-IBD). CGD is caused by inherited defects in any one of the 5 subunits forming the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived ROS production. While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection in this immune compromised population. Understanding the impact of NOX2 defects on the composition and function of the intestinal microbiota may lead to the identification of treatments for CGD-IBD. Methods: We evaluated GI symptom and quality of life scores, and clinical biomarkers of local (i.e. fecal occult blood and calprotectin) and systemic (i.e. CBC, CRP, ESR, and albumin) inflammation in a cohort of 79 patients with CGD, 8 mutation carriers and 17 healthy controls followed at the National Institutes of Health (NIH). We profiled the intestinal microbiome by 16S rRNA (V4 region) sequencing and the stool metabolome by mass spectrometry in all fecal samples, and further validated our findings by profiling the stool microbiome in a second cohort of 36 patients with CGD recruited from 11 centers across North-America through the Primary Immune Deficiency Treatment Consortium (PIDTC). Predictive functional profiling of the microbial communities based on 16S rRNA sequencing was also performed. Results: After controlling for significant variables, we show decreased alpha diversity and identified distinct intestinal microbiome and metabolomic profiles in patients with CGD compared to healthy individuals. In particular, we observed enrichment for Erysipelatoclostridium spp., Sellimonas spp. and Lachnoclostridium spp. in stool samples from patients with CGD. Despite differences in alpha and beta diversity in samples from the NIH compared to the PIDTC cohort, there were several bacterial taxa that correlated significantly between both cohorts. We further demonstrate that patients with active IBD and/or a history of IBD have a distinct microbiome and metabolomic profile compared to patients without CGD-IBD and identified bacterial taxa to be evaluated as potential markers of disease severity, as well as targets for future therapeutic interventions. Conclusions: Intestinal microbiome and metabolomic signatures distinguished patients with CGD and CGD-IBD and identified microbial and metabolomic candidates to be further evaluated as potential targets to improve the management of patients with CGD-IBD.
2023-12-04 | GSE220260 | GEO
Project description:Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit long term use. In the current study using a chronic morphine-murine model a longitudinal approach was undertaken to investigate the role of morphine modulation of gut microbiome as a mechanism contributing to the negative consequences associated with opioids use. The results revealed a significant shift in the gut microbiome and metabolome within 24 hours following morphine treatment when compared to placebo. Morphine induced gut microbial dysbiosis exhibited distinct characteristic signatures profiles including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance. Collectively, these results reveal opioids-induced distinct alteration of gut microbiome, may contribute to opioids-induced pathogenesis. Therapeutics directed at these targets may prolong the efficacy long term opioid use with fewer side effects.
2018-04-16 | E-MTAB-5550 | biostudies-arrayexpress
Project description:Understanding natural defence mechanisms against parasites can be a valuable tool for the development of innovative therapies. In this study, we investigated the interplay between the gill mucus metabolome and microbiome of Chaetodon lunulatus, a butterflyfish known to avoid gill monogeneans whilst living amongst closely related parasitized species. In an attempt to identify metabolites and OTUs potentially involved in parasite defence mechanisms, we studied the metabolome (LC-MS/MS) and microbiome of several sympatric butterflyfish species, including the only non-parasitized species C. lunulatus. After observing significant differences between the metabolome and microbiome of parasitized versus non-parasitized fish (PCoA, ANOSIM), we obtained the discriminant metabolites and OTUs using a supervised analysis. Some of the most important discriminant metabolites were identified as peptides, and three new β-subunit haemoblogin-derived peptides from C. lunulatus (CLHbβ-1, CLHbβ-2 and CLHbβ-3) were purified, characterised and synthesised. We also identified specific bacterial families and OTUs typical from low-oxygen habitats in C. lunulatus gill mucus. By using a correlation network between the two datasets, we found a Fusobacteriaceae strain exclusively present in C. lunulatus highly correlated to the peptides. Finally, we discuss the possible involvement of these peptides and Fusobacteriaceae in monogenean avoidance by this fish species.
2020-11-25 | PXD018867 | Pride
Project description:In a prior report, we observed two distinct lung microbiomes in healthy subjects that we termed â??pneumotypesâ??: pneumotypeSPT, characterized by high bacterial load and supraglottic predominant taxa (SPT) such as the anaerobes Prevotella and Veillonella; and pneumotypeBPT, with low bacterial burden and background predominant taxa (BPT) found in the saline lavage and bronchoscope. Here, we determined the prevalence of these two contrasting lung microbiome types, in a multi-center study of healthy subjects. We confirmed that a lower airway microbiome enriched with upper airway microbes (pneumotypeSPT) was present in ~45% of healthy individuals. Cross-sectional Multicenter cohort. BAL of 49 healthy subjects from three cohort had their lower airway microbiome assessed by 16S rDNA sequencing and microbial gene content (metagenome) was computationally inferred from taxonomic assignments. The amplicons from total 100 samples are barcoded; the barcode and other clinical characteristics (e.g. inflammatory biomarkers and metabolome data) for each sample are provided in the 'Pneumotype.sep.Map.A1.txt' file.
2016-03-29 | E-GEOD-74395 | biostudies-arrayexpress
Project description:RNAseq for non-disease heart LV
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Project description:RNAseq for non-disease heart RV
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Project description:Management of terminal ileal Crohn's disease (CD) is difficult due to fibrotic prognosis and failure to achieve mucosal healing. A limited number of synchronous analyses have been conducted on the transcriptome and microbiome in unpaired terminal ileum tissues. Therefore, our study focused on the transcriptome and mucosal microbiome in terminal ileal tissues of CD patients with the aim of determining the role of cross-talk between the microbiome and transcriptome in the pathogenesis of terminal ileal CD. Mucosa-attached microbial communities were significantly associated with segmental inflammation status. Interaction-related transcription factors (TFs) are the panel nodes for crosstalk between the gene patterns and microbiome for terminal ileal CD. The transcriptome and microbiome in terminal ileal CD can be different related to local inflammatory status, and specific differentially expressed genes (DEGs) may be targeted for mucosal healing. TFs connect gene patterns with the microbiome by reflecting environmental stimuli and signals from microbiota.
2021-04-08 | GSE171244 | GEO
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
2020-11-30 | E-MTAB-8739 | biostudies-arrayexpress
Project description:Colon cancer onset and progression is strongly associated with the presence, absence, or relative abundances of certain microbial taxa in the gastrointestinal tract. However, specific mechanisms affecting disease susceptibility related to complex bacterial mixtures are poorly understood. We used a multi-omics approach to determine how differences in the complex gut microbiome (GM) influence the metabolome and host transcriptome and ultimately affect susceptibility to adenoma development. Fecal samples collected from Pirc rats harboring two distinct complex GMs were analyzed using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). We identified putative metabolite profiles that predicted future disease severity from samples collected prior to observable disease onset. Transcriptome analyses performed after disease onset on normal epithelium and tumor tissues suggests that the GM also alters the host transcriptome. Integrated pathway (IP) analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis was enriched in rats with high tumors (GM:F344) along with increased fatty acid metabolism and mucin biosynthesis. These data emphasize the utility of using untargeted metabolomics to identify metabolites for revealing signatures of susceptibility and resistance.
2018-12-29 | GSE120934 | GEO
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