Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.
Project description:BACKGROUND. Lower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging since non-infectious respiratory illnesses appear clinically similar and existing microbiologic tests are often falsely negative or detect incidentally-carried microbes common in children. These challenges result in antimicrobial overuse and adverse patient outcomes. Lower airway metagenomics has the potential to detect host and microbial signatures of LRTI. Whether it can be applied at scale and in a pediatric population to enable improved diagnosis and precision treatment remains unclear. METHODS. We used tracheal aspirate RNA-sequencing to profile host gene expression and respiratory microbiota in 261 children with acute respiratory failure. We developed a random forest gene expression classifier for LRTI by training on patients with an established diagnosis of LRTI (n=117) or of non-infectious respiratory failure (n=50). We then developed a classifier that integrates the: i) host LRTI probability, ii) abundance of respiratory viruses, and iii) dominance in the lung microbiome of bacteria/fungi considered pathogenic by a rules-based algorithm. RESULTS. The host classifier achieved a median AUC of 0.967 by 5-fold cross-validation, driven by activation markers of T cells, alveolar macrophages and the interferon response. The integrated classifier achieved a median AUC of 0.986 and significantly increased the confidence of patient classifications. When applied to patients with an uncertain diagnosis (n=94), the integrated classifier indicated LRTI in 52% of cases and nominated likely causal pathogens in 98% of those. CONCLUSIONS. Lower airway metagenomics enables accurate LRTI diagnosis and pathogen identification in a heterogeneous cohort of critically ill children through integration of host, pathogen, and microbiome features.
Project description:Microbiome DNA from the adhering fraction of a sheep rumen. The RSTs were generated using an improved version of SARST (referred to as iSARST) from the microbiome DNA extracted from the adhering fraction of the rumen content taken from a sheep. The iSARST method is going to be submitted to Nature Biotechnology for publication. Keywords: other
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
2021-03-03 | GSE168017 | GEO
Project description:Upper/lower respiratory tract microbiome changes patients with COPD
Project description:The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.