Imperial College London

DrMichaelCox

Faculty of MedicineNational Heart & Lung Institute

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 7974michael.cox1 Website

 
 
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Location

 

413Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

57 results found

Groves H, Higham S, Moffatt M, Cox M, Tregoning Jet al., 2019, Respiratory viral infection alters the gut microbiota by inducing inappetence, Publisher: bioRxiv

Abstract The gut microbiota has an important role in health and disease. Respiratory viral infections are extremely common but their impact on the composition and function of the gut microbiota is poorly understood. We previously observed a significant change in the gut microbiota after viral lung infection. Here we show that weight loss during Respiratory Syncytial Virus (RSV) or influenza virus infection was due to decreased food consumption, and that fasting mice independently of infection altered gut microbiota composition. While the acute phase TNF-α response drove early weight loss and inappetence during RSV infection, this was not sufficient to induce changes in the gut microbiota. However, depleting CD8 + cells increased food intake and prevented weight loss resulting in a reversal of the gut microbiota changes normally observed during RSV infection. Viral infection also led to changes in the faecal gut metabolome during RSV infection, with a significant shift in lipid metabolism. Sphingolipids, poly-unsaturated fatty acids (PUFAs) and the short-chain fatty acid (SCFA) valerate all increased in abundance in the faecal metabolome following RSV infection. Whether this, and the impact of infection-induced anorexia on the gut microbiota, are part of a protective, anti-inflammatory response during respiratory viral infections remains to be determined.

Working paper

Ahmed B, Cox MJ, Cuthbertson L, 2019, Growing up with your airway microbiota: a risky business, THORAX, Vol: 74, Pages: 525-526, ISSN: 0040-6376

Journal article

Ahmed B, Cox M, Cuthbertson L, James P, Cookson W, Davies J, Moffatt M, Bush Aet al., 2019, Longitudinal development of the airway microbiota in infants with cystic fibrosis, Scientific Reports, Vol: 9, ISSN: 2045-2322

The pathogenesis of airway infection in cystic fibrosis (CF) is poorly understood. We performed a longitudinal study coupling clinical information with frequent sampling of the microbiota to identify changes in the airway microbiota in infancy that could underpin deterioration and potentially be targeted therapeutically. Thirty infants with CF diagnosed on newborn screening (NBS) were followed for up to two years. Two hundred and forty one throat swabs were collected as a surrogate for lower airway microbiota (median 35 days between study visits) in the largest longitudinal study of the CF oropharyngeal microbiota. Quantitative PCR and Illumina sequencing of the 16S rRNA bacterial gene were performed. Data analyses were conducted in QIIME and Phyloseq in R. Streptococcus spp. and Haemophilus spp. were the most common genera (55% and 12.5% of reads respectively) and were inversely related. Only beta (between sample) diversity changed with age (Bray Curtis r2 = 0.15, P = 0.03). Staphylococcus and Pseudomonas were rarely detected. These results suggest that Streptococcus spp. and Haemophilus spp., may play an important role in early CF. Whether they are protective against infection with more typical CF micro-organisms, or pathogenic and thus meriting treatment needs to be determined.

Journal article

Turek EM, Cox MJ, Hunter M, Hui J, James P, Willis-Owen SAG, Cuthbertson L, James A, Musk AW, Moffatt MF, Cookson WOCMet al., 2019, Distinctive airway microbial ecology of smokers and asthmatics, Publisher: Cold Spring Harbor Laboratory

<jats:p>The airways of the lung carry microbiota that contribute to respiratory health<jats:sup>1</jats:sup>. The ecology of normal airway microbial communities, their responses to environmental events, and the mechanisms through which they cause or modify disease are poorly understood. Cigarette smoking is the dominant malign environmental influence on lung function, causing 11·5% of deaths globally<jats:sup>2</jats:sup>. Asthma is the most prevalent chronic respiratory disease worldwide<jats:sup>3,4</jats:sup>, but was uncommon 100 years ago<jats:sup>5</jats:sup>. The asthma pandemic is linked to urbanization, leading to considerations of protective microbiota loss (the “hygiene hypothesis”)<jats:sup>6-8</jats:sup> and acquisition of strains that may damage the airway epithelia<jats:sup>9</jats:sup>. We therefore investigated oropharyngeal airway microbial community structures in a general population sample of Australian adults. We show here that airway bacterial communities were strongly organized into distinctive co-abundance networks (“guilds”), just seven of which contained 99% of all oropharyngeal operational taxonomic units (OTUs). Smoking was associated with diversity loss, negative effects on abundant taxa, profound alterations to network structure and marked expansion of <jats:italic>Streptococcus</jats:italic> spp.. These perturbations may influence chronic obstructive pulmonary disease<jats:sup>10</jats:sup> (COPD) and lung cancer<jats:sup>11</jats:sup>. In contrast to smokers, the loss of diversity in asthmatics selectively affected low abundance but prevalent OTUs from poorly understood genera such as <jats:italic>Selenomonas, Megasphaera</jats:italic> and <jats:italic>Capnocytophaga</jats:italic>, without coarse scale network disruption. The results open the possibility that replaceme

Working paper

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, MOSAIC Investigators, Moffatt MF, O'Garra A, Openshaw PJMet al., 2019, Author Correction: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza., Nature Immunology, Vol: 20, Pages: 373-373, ISSN: 1529-2908

In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article.

Journal article

Wootton DG, Cox MJ, Gloor GB, Litt D, Hoschler K, German E, Court J, Eneje O, Keogan L, Macfarlane L, Wilks S, Diggles PJ, Woodhead M, Moffatt MF, Cookson WOC, Gordon SBet al., 2019, A haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease, Scientific Reports, Vol: 9, ISSN: 2045-2322

The demographics and comorbidities of patients with community acquired pneumonia (CAP) vary enormously but stratified treatment is difficult because aetiological studies have failed to comprehensively identify the pathogens. Our aim was to describe the bacterial microbiota of CAP and relate these to clinical characteristics in order to inform future trials of treatment stratified by co-morbidity. CAP patients were prospectively recruited at two UK hospitals. We used 16S rRNA gene sequencing to identify the dominant bacteria in sputum and compositional data analysis to determine associations with patient characteristics. We analysed sputum samples from 77 patients and found a Streptococcus sp. and a Haemophilus sp. were the most relatively abundant pathogens. The Haemophilus sp. was more likely to be dominant in patients with pre-existing lung disease, and its relative abundance was associated with qPCR levels of Haemophilus influenzae. The most abundant Streptococcus sp. was associated with qPCR levels of Streptococcus pneumoniae but dominance could not be predicted from clinical characteristics. These data suggest chronic lung disease influences the microbiota of sputum in patients with CAP. This finding could inform a trial of stratifying empirical CAP antibiotics to target Haemophilus spp. in addition to Streptococcus spp. in those with chronic lung disease.

Journal article

Brill SE, James PL, Cuthbertson L, Zhu A, Lawley T, Cookson WOCM, Cox MJ, Wedzicha JA, Moffatt MFet al., 2018, Haemophilus, Antibiotic Therapy and the Airway Microbiome in Chronic Obstructive Pulmonarydisease, Publisher: Cold Spring Harbor Laboratory

<jats:title>ABSTRACT</jats:title><jats:p>Chronic obstructive pulmonary disease (COPD) is a smoking-related illness affecting 64 million people worldwide. Airway infection drives recurrent exacerbations and lung function decline. Prophylactic antibiotics may prevent exacerbations but their use is a significant cause of population antimicrobial resistance.</jats:p><jats:p>We characterised the sputum microbiome by 16S rRNA gene analysis using 138 samples collected during a randomised controlled trial of prophylactic antibiotics in 71 patients with stable COPD. On comparing the profile of the microbiome obtained by sequencing to the isolates grown from samples using standard culture, there were similarities overall, although with a much narrower spectrum of genera on culture with under-representation of certain genera including <jats:italic>Veillonella</jats:italic> and <jats:italic>Prevotella.</jats:italic> There was concordance in the most abundant genera within samples and the number of isolates cultured reflected the measured bacterial diversity.</jats:p><jats:p>We found that at baseline the microbiota of 17 (24%) patients were dominated by <jats:italic>Haemophilus influenzae</jats:italic>, accompanied by narrowed microbial diversity and higher levels of sputum inflammatory cytokines. Different <jats:italic>H. influenzae</jats:italic> strains co-existed within individuals. Opportunistic whole genome sequencing of six <jats:italic>H. influenzae</jats:italic> isolates obtained during the study revealed that all were non-typeable <jats:italic>H. influenzae</jats:italic> (NTHI), with a range of different antibiotic resistance gene profiles, but an identical complement of virulence genes.</jats:p><jats:p>Administration of 13 weeks prophylaxis with moxifloxacin, azithromycin or doxycycline revealed distinctive changes in microbial communities for e

Working paper

Ahmed B, Cox MJ, Cuthbertson L, James PL, Cookson WOC, Davies JC, Moffatt MF, Bush Aet al., 2018, Comparison of the upper and lower airway microbiota in children with chronic lung diseases, PLoS ONE, Vol: 13, ISSN: 1932-6203

RationaleThe lower airway microbiota is important in normal immunological development and chronic lung diseases (CLDs). Young children cannot expectorate and because of the uncertainty whether upper airway samples reflect the lower airway microbiota, there have been few longitudinal paediatric studies to date.ObjectivesTo assess whether throat swabs (TS) and cough swabs (CS) are representative of the lower airway microbiota.MethodsTS, CS, bronchoalveolar lavage and bronchial brushings were prospectively collected from 49 children undergoing fibreoptic bronchoscopy for CLDs. Bacterial DNA was extracted and the 16S rRNA gene V4 region sequenced using the Illumina MiSeq.Results5.97 million high quality reads were obtained from 168 samples (47 TS, 37 CS, 42 BALF and 42 bronchial brushings). CS sequenced poorly. At a community level, no difference in alpha diversity (richness, evenness or Shannon Diversity Index) was seen between lower airway samples and TS (P > 0.05). Less than 6.31% of beta diversity variation related to sampling method for TS (P = 0.001). Variation between pathologies and individual patients was greater (20%, 54% respectively P ≤ 0.001) than between TS and lower airway samples. There was strong correlation in the relative abundance of genera between samples (r = 0.78, P < 0.001). Similarity between upper and lower airway samples was observed to be less for individuals where one sample type was dominated by a single organism.ConclusionsAt the community structure level, TS correlate with lower airway samples and distinguish between different CLDs. TS may be a useful sample for the study of the differences in longitudinal changes in the respiratory microbiota between different CLDs. Differences are too great however for TS to be used for clinical decision making.

Journal article

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, OGarra A, Openshaw PJMet al., 2018, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza, Nature Immunology, ISSN: 1529-2916

Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death (‘bacterial’) pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but was able to enhance its development while attenuating the early ‘viral’ signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.

Journal article

Groves HT, Cuthbertson L, James P, Moffatt MF, Cox MJ, Tregoning JSet al., 2018, Respiratory Disease following Viral Lung Infection Alters the Murine Gut Microbiota, FRONTIERS IN IMMUNOLOGY, Vol: 9, ISSN: 1664-3224

Alterations in the composition of the gut microbiota have profound effects on human health. Consequently, there is great interest in identifying, characterizing, and understanding factors that initiate these changes. Despite their high prevalence, studies have only recently begun to investigate how viral lung infections have an impact on the gut microbiota. There is also considerable interest in whether the gut microbiota could be manipulated during vaccination to improve efficacy. In this highly controlled study, we aimed to establish the effect of viral lung infection on gut microbiota composition and the gut environment using mouse models of common respiratory pathogens respiratory syncytial virus (RSV) and influenza virus. This was then compared to the effect of live attenuated influenza virus (LAIV) vaccination. Both RSV and influenza virus infection resulted in significantly altered gut microbiota diversity, with an increase in Bacteroidetes and a concomitant decrease in Firmicutes phyla abundance. Although the increase in the Bacteroidetes phylum was consistent across several experiments, differences were observed at the family and operational taxonomic unit level. This suggests a change in gut conditions after viral lung infection that favors Bacteroidetes outgrowth but not individual families. No change in gut microbiota composition was observed after LAIV vaccination, suggesting that the driver of gut microbiota change is specific to live viral infection. Viral lung infections also resulted in an increase in fecal lipocalin-2, suggesting low-grade gut inflammation, and colonic Muc5ac levels. Owing to the important role that mucus plays in the gut environment, this may explain the changes in microbiota composition observed. This study demonstrates that the gut microbiota and the gut environment are altered following viral lung infections and that these changes are not observed during vaccination. Whether increased mucin levels and gut inflammation drive, or

Journal article

Cookson WOCM, Cox MJ, Moffatt MF, 2017, New opportunities for managing acute and chronic lung infections., Nature Reviews Microbiology, Vol: 16, Pages: 111-120, ISSN: 1740-1526

Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.

Journal article

Cox MJ, 2017, Ventilator-associated pneumonia: when is a pathogen not a pathogen?, Thorax, Vol: 72, Pages: 774-775, ISSN: 1468-3296

Journal article

Cox MJ, Turek EM, Hennessy C, Mirza GK, James PL, Coleman M, Jones A, Wilson R, Bilton D, Cookson WOC, Moffatt MF, Loebinger MRet al., 2017, Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-cystic fibrosis bronchiectasis patients, PLOS ONE, Vol: 12, ISSN: 1932-6203

Background:Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression. However, the evidence base for antibiotic therapy is limited. DNA based methods offer better identification and quantification of microbial constituents of sputum than standard clinical culture and may help inform patient management strategies. Our study objective was to determine the longitudinal variability of the non-cystic fibrosis (CF) bronchiectasis microbiome in sputum with respect to clinical variables. Eighty-five patients with non-CF bronchiectasis and daily sputum production were recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical measurements were taken, together with additional samples during exacerbations. 16S rRNA gene sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed in conjunction with clinical data.Results:Microbial communities were highly individual in composition and stability, usually with limited diversity and often containing multiple pathogens. When compared to DNA sequencing, microbial culture had restricted sensitivity in identifying common pathogens such as Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis. With some exceptions, community characteristics showed poor correlations with clinical features including underlying disease, antibiotic use and exacerbations, with the subject showing the strongest association with community structure. When present, the pathogens mucoid Pseudomonas aeruginosa and Haemophilus influenzae may also shape the structure of the rest of the microbial community.Conclusions:The use of microbial community analysis of sputum added to information from microbial culture. A simple model of exacerbations driven by bacterial overgrowth was not supported, suggesting a need for revision of principles for antibiotic therapy. In individual patients, the management of chronic bronchial infection may be imp

Journal article

Molyneaux PL, Cox MJ, Wells AU, Kim HC, Ji W, Cookson WOC, Moffatt MF, Kim DS, Maher TMet al., 2017, Changes in the respiratory microbiome during acute exacerbations of idiopathic pulmonary fibrosis, Respiratory Research, Vol: 18, ISSN: 1465-9921

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) have been defined as events of clinically significant respiratory deterioration with an unidentifiable cause. They carry a significant mortality and morbidity and while their exact pathogenesis remains unclear, the possibility remains that hidden infection may play a role. The aim of this pilot study was to determine whether changes in the respiratory microbiota occur during an AE-IPF. Bacterial DNA was extracted from bronchoalveolar lavage from patients with stable IPF and those experiencing an AE-IPF. A hyper-variable region of the 16S ribosomal RNA gene (16S rRNA) was amplified, quantified and pyrosequenced. Culture independent techniques demonstrate AE-IPF is associated with an increased BAL bacterial burden compared to stable disease and highlight shifts in the composition of the respiratory microbiota during an AE-IPF.

Journal article

Molyneaux PL, Willis Owen SA, Cox MJ, James P, Cowman S, Loebinger M, Blanchard A, Edwards LM, Stock C, Daccord C, Renzoni EA, Wells AU, Moffatt MF, Cookson WO, Maher TMet al., 2017, Host-microbial interactions in idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1640-1650, ISSN: 1535-4970

RATIONALE: Changes in the respiratory microbiome are associated with disease progression in Idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome however remains unknown. OBJECTIVES: To explore the host-microbial interaction in IPF. METHODS: Sixty patients diagnosed with IPF were prospectively enrolled, together with 20 matched controls. Subjects underwent bronchoalveolar lavage (BAL) and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For IPF subjects additional samples were taken at 1, 3, and 6 months and (if alive) a year. Gene expression profiles were generated using Affymetrix Human Gene1.1ST Arrays. MEASUREMENTS AND MAIN RESULTS: Network analysis of gene expression data identified two gene modules that strongly associate with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative PCR) and specific microbial OTUs, as well as lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defence response include NLRC4, PGLYRP1, MMP9, DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal over expression in subjects experiencing disease progression, further strengthening their relationship with disease. CONCLUSIONS: Integrated analysis of the host transcriptome and microbial signatures demonstrates an apparent host response to the presence of an altered or more abundant microbiome. These responses remain elevated on longitudinal follow up, suggesting that the bacterial communities of the lower airways may be acting as persistent stimuli for repetitive alveolar injury in IPF.

Journal article

Molyneaux PL, James P, Cuthbertson L, Cox MJ, Kim D, Maher TM, Cookson W, Moffatt Met al., 2017, The Role Of The Fungal Mycobiome In Ipf, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Ahmed B, Cox MJ, Cuthbertson L, James P, Cookson WO, Davies JC, Moffatt MF, Bush Aet al., 2016, EARLY DEVELOPMENT OF THE AIRWAY MICROBIOTA IN INFANTS WITH CF, PEDIATRIC PULMONOLOGY, Vol: 51, Pages: 328-328, ISSN: 8755-6863

Journal article

Depner M, Ege MJ, Cox MJ, Dwyer S, Walker AW, Birzele LT, Genuneit J, Horak E, Braun-Fahrländer C, Danielewicz H, Maier RM, Moffatt MF, Cookson WO, Heederik D, von Mutius E, Legatzki Aet al., 2016, Bacterial microbiota of the upper respiratory tract and childhood asthma, Journal of Allergy and Clinical Immunology, ISSN: 1097-6825

BACKGROUND: Patients with asthma and healthy controls differ in bacterial colonization of the respiratory tract. The upper airways have been shown to reflect colonization of the lower airways, the actual site of inflammation in asthma, which is hardly accessible in population studies. OBJECTIVE: We sought to characterize the bacterial communities at 2 sites of the upper respiratory tract obtained from children from a rural area and to relate these to asthma. METHODS: The microbiota of 327 throat and 68 nasal samples from school-age farm and nonfarm children were analyzed by 454-pyrosequencing of the bacterial 16S ribosomal RNA gene. RESULTS: Alterations in nasal microbiota but not of throat microbiota were associated with asthma. Children with asthma had lower α- and β-diversity of the nasal microbiota as compared with healthy control children. Furthermore, asthma presence was positively associated with a specific operational taxonomic unit from the genus Moraxella in children not exposed to farming, whereas in farm children Moraxella colonization was unrelated to asthma. In nonfarm children, Moraxella colonization explained the association between bacterial diversity and asthma to a large extent. CONCLUSIONS: Asthma was mainly associated with an altered nasal microbiota characterized by lower diversity and Moraxella abundance. Children living on farms might not be susceptible to the disadvantageous effect of Moraxella. Prospective studies may clarify whether Moraxella outgrowth is a cause or a consequence of loss in diversity.

Journal article

Cox MJ, Turek EM, Hennessy C, Mirza GK, James PL, Coleman M, Jones A, Wilson R, Bilton D, Cookson WOC, Moffatt MF, Loebinger Met al., 2016, Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-CF bronchiectasis patients, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression. However, the evidence base for antibiotic therapy is limited. DNA based methods offer better identification and quantification of microbial constituents of sputum than standard clinical culture and may help inform patient management strategies. Our study objective was to determine the longitudinal variability of the non-CF bronchiectasis microbiome in sputum with respect to clinical variables.</jats:p><jats:p>Eighty-five patients with non-cystic fibrosis (CF) bronchiectasis and daily sputum production were recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical measurements were taken, together with additional samples during exacerbations. 16S rRNA gene sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed in conjunction with clinical data.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Microbial communities were highly individual in composition and stability, usually with limited diversity and often containing multiple pathogens. When compared to DNA sequencing, microbial culture had restricted sensitivity in identifying common pathogens. With some exceptions, community characteristics showed poor correlations with clinical features including underlying disease, antibiotic use and exacerbations, with the subject showing the strongest association with community structure. When present, certain pathogens may also shape the structure of the rest of the microbial community.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The use of microbial community analysis of sputum added to information from microbial culture. A simple model of exacerbat

Working paper

Zhang Q, Cox M, Liang Z, Brinkmann F, Cardenas PA, Duff R, Bhavsar P, Cookson W, Moffatt M, Chung KFet al., 2016, Airway microbiota in severe asthma and relationship to asthma severity and phenotypes, PLOS One, Vol: 11, ISSN: 1932-6203

Background: The lower airways harbor a community of bacterial species which is altered in asthma. Objectives: We examined whether the lower airway microbiota were related to measures of asthma severityMethods: We prospectively recruited 26 severe asthma, 18 non-severe asthma and 12 healthy subjects. DNA was extracted from induced sputum and PCR amplification of the V3-V5 region of bacterial 16S rRNA gene was performed. Results: We obtained 138,218 high quality sequences which were rarefied at 133 sequences/sample. Twenty OTUs had sequences ≥1% of total. There were marked differences in the distribution of Phyla between groups (P=2.8x10-118). Bacteroidetes and Fusobacteria were reduced in non-severe and severe asthmatic groups. Proteobacteria were more common in non-severe asthmatics compared to controls (OR=2.26; 95% CI=1.94-2.64) and Firmicutes were increased in severe asthmatics compared to controls (OR=2.15; 95%CI=1.89-2.45). Streptococcal OTUs amongst the Firmicutes were associated with recent onset asthma, rhinosinusitis and sputum eosinophilia.Conclusions: Sputum microbiota in severe asthma differs from healthy controls and non-severe asthmatics, and is characterized by the presence of Streptococcus spp with eosinophilia. Whether these organisms are causative for the pathophysiology of asthma remains to be determined.

Journal article

Cox MJ, Moffatt MF, Cookson WOC, 2015, Outside In: Sequencing the Lung Microbiome, American Journal of Respiratory and Critical Care Medicine, Vol: 192, Pages: 403-404, ISSN: 1535-4970

Journal article

Shaw AG, Sim K, Randell P, Cox M, McClure Z, Li MS, Donaldson H, Langford P, Cookson WOCM, Moffatt MF, Kroll JSet al., 2015, Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants, PLOS One, Vol: 10, ISSN: 1932-6203

Journal article

Annamalay AA, James P, Cowman S, Abbott S, Zhang G, Sikazwe C, Khoo S-K, Bizzintino J, Chidlow G, Cox MJ, Moffatt M, Green RJ, Cookson WO, LeSouef PNet al., 2015, Nontuberculous Mycobacteria In Young South African Children With Acute Lower Respiratory Infections, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Wootton DG, Cox MJ, Hickey GL, Eneje O, Court J, Macfarlane L, Wilks S, Woodhead M, Cookson WO, Moffatt MF, Diggle PJ, Gordon SBet al., 2015, The Genus Haemophilus Was Dominant In A Cohort With Community Acquired Pneumonia And Low Species Diversity Was Related To Age And Prior Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Cox MJ, Salter SJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AWet 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

Conference paper

Molyneaux PL, Cox MJ, Cookson WO, Moffatt MF, Kim DS, Maher TMet 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

Conference paper

Cox MJ, Turek EM, Mirza GK, James PL, Hennessey C, Coleman M, Jones A, Wilson R, Bilton D, Cookson WO, Moffatt MF, Loebinger MRet 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

Conference paper

Ahmed B, Cox MJ, Cookson WOC, Davies JC, Moffatt MF, Bush Aet 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

Conference paper

CFelton I, Benson I, Nicholson A, Al-Shafi K, James P, Cox MJ, Walley AJ, Moffatt MF, Bilton D, Loebinger MR, Simmonds NJ, Cookson WOet 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

Conference paper

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