Project description:In this study, we assessed lower airway microbiome from a cohort of patients to determine whether specific microbiome taxa correlate with with specific metabolic activities. In a subset of 12 patients, transcriptomic expression were analyzed to compare host mucosa immune response We collected peripheral airway brushings from the 12 subjects whose lung microbiome were analyzed; Total RNA were obtained from the peripheral airway epithelium.
Project description:Non-cystic fibrosis bronchiectasis is a severe respiratory disease characterized by progressive loss of lung function, resulting in high morbidity and even early mortality. Current treatments cannot repair progressive lung damage, which encouraged the exploration of stem and progenitor cell-based regenerative therapies. In current study, we found that the P63+ progenitor cells normally located in airway basal layer could appear in the alveolar spaces of bronchiectasis patients. We successfully cloned and expanded the progenitor cells from the airway brushing tissues of patients. Then we conducted a randomized, single-blind, controlled, phase 1/2 trial to evaluate the safety and efficacy of autologous P63+ progenitor cells transplantation in bronchiectasis patients.
Project description:In this study, we assessed lower airway microbiome from a cohort of patients to determine whether specific microbiome taxa correlate with with specific metabolic activities. In a subset of 12 patients, transcriptomic expression were analyzed to compare host mucosa immune response
Project description:Our findings have clinical implications. Identification of sputum exosomal miRNA helps explore the important biological pathways underlying the pathogenesis of bronchiectasis, thus unraveling candidate targets for future interventions of PA colonization. Apart from canonical inflammatory pathways, we have unraveled the modulation of longevity regulation pathway which opens a new avenue for exploring how PA colonization interacts with the airway epithelium. The significant correlation between sputum inflammatory biomarkers and miR-92b-5p and miR-223-3p provided further evidence on the unresolved inflammation in the PA-colonized microenvironment. However, causality cannot be inferred based on the current study design.
Project description:Limited CITE-seq antibody panel and 5' gene expression profiling of human nasopharyngeal cells collected with flocked swabs, paired with TCR and BCR sequencing of NP lymphocytes. FACS-sorted SARS-CoV-2 antigen-specific memory B and T cells with 5' gene expression profiling and scBCR and scTCRseq.
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:A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How the lung microbiome evolves over time, and whether changes within the microbiome correlate with future disease progression is not yet known. We assessed the microbial community structure of 133 serial sputa and subsequent disease course of 29 nCFB patients collected over a span of 4-16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in the microbial community of individuals were observed during extended follow-up suggesting the microbiome remains relatively stable over prolonged periods. Samples that were Pseudomonas aeruginosa culture positive displayed markedly different microbial community structures compared to those that were positive for Haemophilus influenzae. Importantly, patients with sputum of lower microbial community diversity were more likely to experience subsequent lung function decline as defined by annual change in ≥-1 FEV1% predicted. Shannon diversity values <1 were more prevalent in patients with FEV1 decline (P = 0.002). However, the relative abundance of particular core microbiota constituents did not associate with risk of decline. Here we present data confirming that the microbiome of nCFB individuals is generally stable, and that microbiome-based measurements may have a prognostic role as biomarkers for nCFB.
Project description:IntroductionNon-cystic fibrosis bronchiectasis is a respiratory health condition with many possible aetiologies, some of which are potentially reversible in childhood with early diagnosis and appropriate treatment. It is important to understand factors which contribute to progression or potential resolution of bronchiectasis. It is evident that respiratory exacerbations are a key feature of bronchiectasis disease progression. In this pilot study we document how the microbiota of the upper and lower airways presents during the course of an exacerbation and treatment.MethodsWe recruited children (aged 1-15) undergoing antibiotic treatment for bronchiectasis exacerbations at Starship Children's Hospital and outpatient clinics. Sputum and nasal swabs were taken before and after antibiotic treatment. Sample DNA was extracted, then bacterial 16S rRNA genes amplified and sequenced via Illumina MiSeq.ResultsThirty patients were recruited into this study with 81 samples contributing to the final dataset, including 8 patients with complete sets of upper and lower airway samples at both (before and after antibiotics) timepoints. Changes in alpha-diversity over the course of an exacerbation and treatment were non-significant. However, sample composition did alter over the course of an exacerbation, with most notably a reduction in the relative abundance of amplicon sequence variants assigned to Haemophilus.DiscussionHaemophilus has been associated with more severe symptoms in respiratory infections and a reduction in its relative abundance may represent a positive shift in a patient's microbiota. Current treatments for bronchiectasis may preserve bacterial diversity while altering microbiota composition.