Publications
396 results found
Cardenas PA, Cookson WOC, 2015, The Microbiome at Other Mucosal Sites, Mucosal Immunology: Fourth Edition, Pages: 79-94, ISBN: 9780124158474
Culture-independent studies of the microbiome of mucosal sites other than the intestine are at an early and exciting stage. Mucosal surfaces are universally warm and moist and often contiguous with or adjacent to each other and the upper or lower gastrointestinal tract. The microbiome at different sites may share common elements as well as possessing distinct and characteristic members. The impression from the limited number of studies currently available is that each site may possess a surprisingly consistent core microbiome that is shared by most individuals. This consistency is likely to reflect almost completely unexplored host factors that actively manage the microbiome. In the place of a simplistic model that pathogens cause disease, microbial-induced injuries may now be understood in terms of complex changes in a dynamic and innately homeostatic community. Therefore, in this review, we discuss what is known about the normal microbiome at each site, before exploring changes in the microbiome that accompany or cause disease. The emphasis of the review is on the bacterial microbiome only because of the limited nature of investigation into normal viral and fungal communities at human mucosal sites.
Sim K, Shaw AG, Randell P, et al., 2015, Dysbiosis anticipating necrotizing enterocolitis in very premature infants, Clinical Infectious Diseases, Vol: 60, Pages: 389-397, ISSN: 1537-6591
Background. Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel disease of premature infants speculatively associated with infection. Suspected NEC can be indistinguishable from sepsis, and in established cases an infant may die within hours of diagnosis. Present treatment is supportive. A means of presymptomatic diagnosis is urgently needed. We aimed to identify microbial signatures in the gastrointestinal microbiota preceding NEC diagnosis in premature infants.Methods. Fecal samples and clinical data were collected from a 2-year cohort of 369 premature neonates. Next-generation sequencing of 16S ribosomal RNA gene regions was used to characterize the microbiota of prediagnosis fecal samples from 12 neonates with NEC, 8 with suspected NEC, and 44 controls. Logistic regression was used to determine clinical characteristics and operational taxonomic units (OTUs) discriminating cases from controls. Samples were cultured and isolates identified using matrix-assisted laser desorption/ionization–time of flight. Clostridial isolates were typed and toxin genes detected.Results. A clostridial OTU was overabundant in prediagnosis samples from infants with established NEC (P = .006). Culture confirmed the presence of Clostridium perfringens type A. Fluorescent amplified fragment-length polymorphism typing established that no isolates were identical. Prediagnosis samples from NEC infants not carrying profuse C. perfringens revealed an overabundance of a Klebsiella OTU (P = .049). Prolonged continuous positive airway pressure (CPAP) therapy with supplemental oxygen was also associated with increased NEC risk.Conclusions. Two fecal microbiota signatures (Clostridium and Klebsiella OTUs) and need for prolonged CPAP oxygen signal increased risk of NEC in presymptomatic infants. These biomarkers will assist development of a screening tool to allow very early diagnosis of NEC.Clinical Trials Registration. NCT01102738.
Brill SE, James P, Cookson WOC, et al., 2015, Comparison Of Quantitative Culture And 16s Qpcr For Quantification Of Total Airway Bacterial Load In Chronic Obstructive Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Cox MJ, Turek EM, Mirza GK, et al., 2015, Longitudinal Analysis Of The Non-Cystic Fibrosis Bronchiectasis Microbiome, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Cox MJ, Salter SJ, Turek EM, et al., 2015, Contamination Of Reagents Can Critically Impact Sequence-Based Microbiome Studies, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Molyneaux PL, Cox MJ, Cookson WO, et al., 2015, Changes In The Respiratory Microbiome During Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Zhang Y, Dean C, Chessum L, et al., 2014, Functional analysis of a novel ENU-induced PHD finger 11 (<i>Phf11)</i> mouse mutant, MAMMALIAN GENOME, Vol: 25, Pages: 573-582, ISSN: 0938-8990
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- Citations: 2
Ahmed B, Cox MJ, Cookson WOC, et al., 2014, COMPARISON OF THE UPPER AND LOWER AIRWAY MICROBIOTA IN CHILDREN, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A123-A123, ISSN: 0040-6376
Loeser S, Zhang Y, Gregory L, et al., 2014, Novel insights into the <i>in vivo</i> function of <i>Ormdl3</i> - a gene associated with the onset of childhood asthma, IMMUNOLOGY, Vol: 143, Pages: 59-59, ISSN: 0019-2805
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- Citations: 3
CFelton I, Benson I, Nicholson A, et al., 2014, PRELIMINARY EVALUATION OF THE FUNGAL AIRWAY MICROBIOME IN ADULT CYSTIC FIBROSIS BY NEXT-GENERATION SEQUENCING, CULTURE AND STAINING TECHNIQUES, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A164-A164, ISSN: 0040-6376
Salter SJ, Cox MJ, Turek EM, et al., 2014, Reagent and laboratory contamination can critically impact sequence-based microbiome analyses, BMC Biology, Vol: 12, ISSN: 1741-7007
BackgroundThe study of microbial communities has been revolutionised in recent years by the widespread adoption of culture independent analytical techniques such as 16S rRNA gene sequencing and metagenomics. One potential confounder of these sequence-based approaches is the presence of contamination in DNA extraction kits and other laboratory reagents.ResultsIn this study we demonstrate that contaminating DNA is ubiquitous in commonly used DNA extraction kits and other laboratory reagents, varies greatly in composition between different kits and kit batches, and that this contamination critically impacts results obtained from samples containing a low microbial biomass. Contamination impacts both PCR-based 16S rRNA gene surveys and shotgun metagenomics. We provide an extensive list of potential contaminating genera, and guidelines on how to mitigate the effects of contamination.ConclusionsThese results suggest that caution should be advised when applying sequence-based techniques to the study of microbiota present in low biomass environments. Concurrent sequencing of negative control samples is strongly advised.
Molyneaux PL, Cox MJ, Willis-Owen SAG, et al., 2014, The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 906-913, ISSN: 1535-4970
Rationale:Idiopathic pulmonaryfibrosis (IPF)isa progressivelung diseaseof unknown cause that leads to respiratory failure and death within 5 yearsof diagnosis. Overt respiratory infection and immunosuppression carrya high morbidity and mortality, and polymorphisms in genes related toepithelial integrity and host defense predispose to IPF.Objectives: To investigate the role of bacteria in the pathogenesisand progression of IPF.Methods: We prospectively enrolled patients diagnosed with IPFaccording to international criteria together with healthy smokers,nonsmokers, and subjectswithmoderate chronic obstructive pulmonarydisease as control subjects. Subjects underwent bronchoalveolarlavage (BAL), from which genomic DNA was isolated. The V3–V5region of the bacterial 16S rRNA gene was amplified, allowingquantification of bacterial load and identification of communities by 16SrRNA quantitative polymerase chain reaction and pyrosequencing. Measurements and Main Results: Sixty-five patients with IPFhad double the burden of bacteria in BAL fluid compared with 44 controlsubjects. Baseline bacterial burden predicted the rate of decline in lungvolume and risk of death and associated independently with thers35705950 polymorphism of the MUC5B mucin gene, a proven hostsusceptibilityfactorfor IPF. Sequencing yielded912,883 high-quality readsfrom all subjects.WeidentifiedHaemophilus, Streptococcus,Neisseria, andVeillonella spp. to be more abundant in cases than control subjects.Regression analyses indicated that these specific operational taxonomicunits as well as bacterial burden associated independently with IPF.Conclusions: IPF is characterized by an increased bacterial burdenin BAL that predicts decline in lung function and death. Trials ofantimicrobial therapy are needed to determine if microbial burdenis pathogenic in the disease.
Liang L, Cookson WOC, 2014, Grasping nettles: cellular heterogeneity and other confounders in epigenome-wide association studies, HUMAN MOLECULAR GENETICS, Vol: 23, Pages: R83-R88, ISSN: 0964-6906
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- Citations: 34
Dizier M-H, Margaritte-Jeannin P, Madore A-M, et al., 2014, The nuclear factor I/A (<i>NFIA</i>) gene is associated with the asthma plus rhinitis phenotype, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 134, Pages: 576-+, ISSN: 0091-6749
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- Citations: 14
Hoggart CJ, Venturini G, Mangino M, et al., 2014, Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index, PLOS Genetics, Vol: 10, ISSN: 1553-7390
The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present anovel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. Themethod exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups.We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six leadSNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternalrs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCRexperiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent onparental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelatedindividuals to identify POEs and demonstrates that they play an important role in adult obesity.
Salter, Susannah Cox, Michael J Turek, et al., 2014, Reagent contamination can critically impact sequence-based microbiome analyses, bioRxiv
Susannah Salter1,7 (sb18{at}sanger.ac.uk), Michael J Cox2 (michael.cox1{at}imperial.ac.uk), Elena M Turek2 (elena.turek11{at}imperial.ac.uk), Szymon T Calus3 (s.t.calus{at}bham.ac.uk), William O Cookson2 (w.cookson{at}imperial.ac.uk), Miriam F Moffatt2 (m.moffatt{at}imperial.ac.uk), Paul Turner4 (pault{at}tropmedres.ac), Julian Parkhill5 (parkhill{at}sanger.ac.uk), Nick Loman3 (n.j.loman{at}bham.ac.uk) and Alan W Walker6 (alan.walker{at}abdn.ac.uk) 1 Wellcome Trust Sanger Institute; 2 Molecular Genetics and Genomics, National Heart and Lung Institute, Imperial College London; 3 Institute of Microbiology and Infection, University of Birmingham; 4 Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford; 5 Pathogen Genomics, Wellcome Trust Sanger Institute; 6 Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen ↵* Corresponding author; email: sb18{at}sanger.ac.uk AbstractThe study of microbial communities has been revolutionised in recent years by the widespread adoption of culture independent analytical techniques such as 16S rRNA gene sequencing and metagenomics. One potential confounder of these sequence-based approaches is the presence of contamination in DNA extraction kits and other laboratory reagents. In this study we demonstrate that contaminating DNA is ubiquitous in commonly used DNA extraction kits, varies greatly in composition between different kits and kit batches, and that this contamination critically impacts results obtained from samples containing a low microbial biomass. Contamination impacts both PCR-based 16S rRNA gene surveys and shotgun metagenomics. These results suggest that caution should be advised when applying sequence-based techniques to the study of microbiota present in low biomass environments. We provide an extensive list of potential contaminating genera, and guidelines on how to mitigate the effects of contamination. Concurrent sequencing of negative control samples i
van der Valk RJP, Duijts L, Timpson NJ, et al., 2014, Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 134, Pages: 46-55, ISSN: 0091-6749
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- Citations: 30
Naeem A, Zhu Y, Moffat M, et al., 2014, The mTORC1 protein Raptor controls filaggrin levels through an Akt1/cathepsin H dependent mechanism, Annual Meeting of the Society-for-Investigative-Dermatology (SID), Publisher: NATURE PUBLISHING GROUP, Pages: S63-S63, ISSN: 0022-202X
Ma B, Wilker EH, Willis-Owen SAG, et al., 2014, Predicting DNA methylation level across human tissues, NUCLEIC ACIDS RESEARCH, Vol: 42, Pages: 3515-3528, ISSN: 0305-1048
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- Citations: 72
Weidinger S, Willis-Owen SA, Kamatani Y, et al., 2014, A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis, 41st Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung (ADF), Publisher: WILEY, Pages: E21-E21, ISSN: 0906-6705
Scholtens S, Postma DS, Moffatt MF, et al., 2014, Novel childhood asthma genes interact with <i>in utero</i> and early-life tobacco smoke exposure, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 133, Pages: 885-888, ISSN: 0091-6749
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- Citations: 36
Weidinger S, Willis-Owen SAG, Kamatani Y, et al., 2013, A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis, Human Molecular Genetics, Vol: 22, Pages: 4841-4856, ISSN: 0964-6906
Atopic dermatitis (AD) is the most common dermatological disease of childhood. Many children with AD have asthma and AD shares regions of genetic linkage with psoriasis, another chronic inflammatory skin disease. We present here a genome-wide association study (GWAS) of childhood-onset AD in 1563 European cases with known asthma status and 4054 European controls. Using Illumina genotyping followed by imputation, we generated 268 034 consensus genotypes and in excess of 2 million single nucleotide polymorphisms (SNPs) for analysis. Association signals were assessed for replication in a second panel of 2286 European cases and 3160 European controls. Four loci achieved genome-wide significance for AD and replicated consistently across all cohorts. These included the epidermal differentiation complex (EDC) on chromosome 1, the genomic region proximal to LRRC32 on chromosome 11, the RAD50/IL13 locus on chromosome 5 and the major histocompatibility complex (MHC) on chromosome 6; reflecting action of classical HLA alleles. We observed variation in the contribution towards co-morbid asthma for these regions of association. We further explored the genetic relationship between AD, asthma and psoriasis by examining previously identified susceptibility SNPs for these diseases. We found considerable overlap between AD and psoriasis together with variable coincidence between allergic rhinitis (AR) and asthma. Our results indicate that the pathogenesis of AD incorporates immune and epidermal barrier defects with combinations of specific and overlapping effects at individual loci.
Molyneaux PL, Cox MJ, Mallia P, et al., 2013, THE ROLE OF THE RESPIRATORY MICROBIOME IN IDIOPATHIC PULMONARY FIBROSIS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A22-A22, ISSN: 0040-6376
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- Citations: 2
Molyneaux PL, Mallia P, Cox MJ, et al., 2013, Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 188, Pages: 1224-1231, ISSN: 1073-449X
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- Citations: 262
Cox MJ, Cookson WOCM, Moffatt MF, 2013, Sequencing the human microbiome in health and disease, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: R88-R94, ISSN: 0964-6906
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- Citations: 89
Cardenas P, Cooper P, Moffatt M, et al., 2013, The development of the upper respiratory microbiome on infancy and the dysbiosis related with wheezing syndrome and health on children from the rural tropics of Ecuador, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
Hu Y-J, Berndt SI, Gustafsson S, et al., 2013, Meta-analysis of Gene-Level Associations for Rare Variants Based on Single-Variant Statistics, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 93, Pages: 236-248, ISSN: 0002-9297
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- Citations: 53
Esparza-Gordillo J, Schaarschmidt H, Liang L, et al., 2013, A functional IL-6 receptor (<i>IL6R</i>) variant is a risk factor for persistent atopic dermatitis, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 132, Pages: 371-377, ISSN: 0091-6749
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- Citations: 66
Cookson WOC, Moffatt MF, 2013, Bedside to Gene and Back in Idiopathic Pulmonary Fibrosis, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 368, Pages: 2228-2230, ISSN: 0028-4793
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- Citations: 6
Berndt SI, Gustafsson S, Maegi R, et al., 2013, Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture, NATURE GENETICS, Vol: 45, Pages: 501-U69, ISSN: 1061-4036
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- Citations: 443
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