Project description:Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity. Overall design: 104 total samples; 81 are RSV, of which 20 are outpatient and 61 are inpatient; 23 healthy age-matched controls. No technical replicates. 41 of the samples are from a batch run in 2015, the remaining 63 were run in a batch in 2011.
Project description:This study compared the subgingival microbiota of subjects with periodontitis to those with periodontal health using the Human Oral Microbe Identification Microarray (HOMIM). Overall design: The microbial profiles of subgingival plaque from healthy and periodontitis subjects was compared using community network analysis.
Project description:Xiangjiang River (Hunan, China) has been contaminated with heavy metal for several decades by surrounding factories. However, little is known about the influence of a gradient of heavy metal contamination on the diversity, structure of microbial functional gene in sediment. To deeply understand the impact of heavy metal contamination on microbial community, a comprehensive functional gene array (GeoChip 5.0) has been used to study the functional genes structure, composition, diversity and metabolic potential of microbial community from three heavy metal polluted sites of Xiangjiang River. Three groups of samples, A, B and C. Every group has 3 replicates.
Project description:Significant gut microbiota heterogeneity exists amongst UC patients though the clinical implications of this variance are unknown. European and South Asian UC patients exhibit distinct disease risk alleles, many of which regulate immune function and relate to variation in gut microbiota β-diversity. We hypothesized ethnically distinct UC patients exhibit discrete gut microbiotas with unique luminal metabolic programming that influence adaptive immune responses and relate to clinical status. Using parallel bacterial 16S rRNA and fungal ITS2 sequencing of fecal samples (UC n=30; healthy n=13), we corroborated previous observations of UC-associated depletion of bacterial diversity and demonstrated significant gastrointestinal expansion of Saccharomycetales as a novel UC characteristic. We identified four distinct microbial community states (MCS 1-4), confirmed their existence using microbiota data from an independent UC cohort, and show they co-associate with patient ethnicity and degree of disease severity. Each MCS was predicted to be uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of metabolic products from these pathways. Using a novel in vitro human DC/T-cell assay we show that DC exposure to patient fecal water led to MCS -specific changes in T-cell populations, particularly the Th1:Th2 ratio, and that patients with the most severe disease exhibited the greatest Th2 skewing. Thus, based on ethnicity, microbiome composition, and associated metabolic dysfunction, UC patients may be stratified in a clinically and immunologically meaningful manner, providing a platform for the development of FMC-focused therapy. Fecal microbiome was assessed with Affymetrix PhyloChip arrays from patients with ulcerative colitis and healthy controls.
Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy. We used G3 PhyloChip microarrays (commercially available from Second Genome, Inc.) to profile gut bacteria in rectosigmoid biopsies from 32 subjects: 6 HIV-infected viremic untreated (VU), 18 HIV-infected subjects on highly active antiretroviral therapy (HAART), 1 HIV-infected long-term non-progressor that is untreated (LTNP), and 9 HIV-uninfected subjects (HIV-).
Project description:The increased urban pressures are often associated with specialization of microbial communities. Microbial communities being a critical player in the geochemical processes, makes it important to identify key environmental parameters that influence the community structure and its function.In this proect we study the influence of land use type and environmental parameters on the structure and function of microbial communities. The present study was conducted in an urban catchment, where the metal and pollutants levels are under allowable limits. The overall goal of this study is to understand the role of engineered physicochemical environment on the structure and function of microbial communities in urban storm-water canals. Microbial community structure was determined using PhyoChio (G3) Water and sediment samples were collected after a rain event from Sungei Ulu Pandan watershed of >25km2, which has two major land use types: Residential and industrial. Samples were analyzed for physicochemical variables and microbial community structure and composition. Microbial community structure was determined using PhyoChio (G3)
Project description:The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used ATAC-seq to define chromatin accessibility in predicted enhancer regions of intestinal αβ+ and γδ+ intraepithelial lymphocytes (IELs) purified from germ-free mice, their conventionally-raised (CONV-R) counterparts, and mice reared GF and then colonized with a CONV-R gut microbiota at the end of the suckling-weaning transition. Characterizing genes adjacent to traditional enhancers and super-enhancers revealed signaling networks, metabolic pathways, and enhancer-associated transcription factors affected by the microbiota. Our results support the notion that epigenetic modifications help define microbial community-affiliated functional features of host immune cell lineages. Overall design: We interrogated chromatin accessibility using ATAC-seq in four cell types derived from mice (CD4+ T cells, CD8+ T cells, αβ+ intraepithelial lymphocytes, and γδ+ intraepithelial lymphocytes), across three gut microbial colonization states (germ-free, conventionally-raised, and conventionalized).
Project description:Cropping soils vary in extent of natural suppression of soil-borne plant diseases. However, it is unknown whether similar variation occurs across pastoral agricultural systems. We examined soil microbial community properties known to be associated with disease suppression across 50 pastoral fields varying in management intensity. The composition and abundance of the disease-suppressive community were assessed from both taxonomic and functional perspectives. Overall design: The genomic DNA was extracted from 50 pastoral fields (1 replicate per soil) varying in management intensity. The DNA from each sample was hybridised to GeoChip 5.0 mciroarrays and processed. The genes associated with the biosynthesis of a suite of secondary metabolites were then investigated
Project description:To study long-term elevated CO2 and enriched N deposition interactive effects on microbial community and soil ecoprocess, here we investigated soil microbial community in a grassland ecosystem subjected to ambient CO2 (aCO2, 368 ppm), elevated CO2 (eCO2, 560 ppm), ambient nitrogen deposition (aN) or elevated nitrogen deposition (eN) treatments for a decade. There exist antagonistic CO2×N interactions on microbial functional genes associated with C, N, P S cycling processes. More strong antagonistic CO2×N interactions are observed on C degradation genes than other genes. Remarkably antagonistic CO2×N interactions on soil microbial communities could enhance soil C accumulation. Overall design: Samples were collected under four different carbon dioxide and nitrogen treatment (aCaN,eCaN,aCeN and eCeN) in each of the four plant species richness levels:1, 4, 9, 16 ; In plots with 1 plant species, each treatment has 32 replicates ; In plots with 4 and 9 plant speices, each treatment has 15 replicates ; In plots with 16 plant species, each treatment has 12 replicates.
Project description:Cloutier2012 - Feedback motif for Parkinson's
This model is described in the article:
Feedback motif for the
pathogenesis of Parkinson's disease.
Cloutier M, Middleton R, Wellstead
IET Syst Biol 2012 Jun; 6(3):
Previous article on the integrative modelling of Parkinson's
disease (PD) described a mathematical model with properties
suggesting that PD pathogenesis is associated with a
feedback-induced biochemical bistability. In this article, the
authors show that the dynamics of the mathematical model can be
extracted and distilled into an equivalent two-state feedback
motif whose stability properties are controlled by
multi-factorial combinations of risk factors and genetic
mutations associated with PD. Based on this finding, the
authors propose a principle for PD pathogenesis in the form of
the switch-like transition of a bistable feedback process from
'healthy' homeostatic levels of reactive oxygen species and the
protein ?-synuclein, to an alternative 'disease' state in which
concentrations of both molecules are stable at the damagingly
high-levels associated with PD. The bistability is analysed
using the rate curves and steady-state response characteristics
of the feedback motif. In particular, the authors show how a
bifurcation in the feedback motif marks the pathogenic moment
at which the 'healthy' state is lost and the 'disease' state is
initiated. Further analysis shows how known risks (such as:
age, toxins and genetic predisposition) modify the stability
characteristics of the feedback motif in a way that is
compatible with known features of PD, and which explain
properties such as: multi-factorial causality, variability in
susceptibility and severity, multi-timescale progression and
the special cases of familial Parkinson's and Parkinsonian
symptoms induced purely by toxic stress.
Stress of 2.6 obtained by optimization
(parameter S1) was imposed between days 10 and 150 in order to
reproduce the Figure.
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