Publications
Results
- Showing results for:
- Reset all filters
Search results
-
Conference paperMcDonald JAK, Mullish BH, Pechlivanis A, et al., 2018,
A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation
, ISME17 -
Journal articleHoyles L, Jiménez-Pranteda MJ, Chilloux J, et al., 2018,
Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota
, Microbiome, Vol: 6, ISSN: 2049-2618Background:The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes.Results:A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture.Conclusions:Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermenta
-
Journal articleBates K, Clare F, O'Hanlon S, et al., 2018,
Amphibian chytridiomycosis outbreak dynamics are linked with host skin bacterial community structure
, Nature Communications, Vol: 9, ISSN: 2041-1723Host-associated microbes are vital for combatting infections and maintaining health. In amphibians, certain skin-associated bacteria inhibit the fungal pathogen Batrachochytrium dendrobatidis (Bd), yet our understanding of host microbial ecology and its role in disease outbreaks is limited. We sampled skin-associated bacteria and Bd from Pyrenean midwife toad populations exhibiting enzootic or epizootic disease dynamics. We demonstrate that bacterial communities differ between life stages with few shared taxa, indicative of restructuring at metamorphosis. We detected a significant effect of infection history on metamorph skin microbiota, with reduced bacterial diversity in epizootic populations and differences in community structure and predicted function. Genome sequencing of Bd isolates supports a single introduction to the Pyrenees and reveals no association between pathogen genetics and epidemiological trends. Our findings provide an ecologically relevant insight into the microbial ecology of amphibian skin and highlight the relative importance of host microbiota and pathogen genetics in predicting disease outcome.
-
Journal articleMoreno-Navarrete JM, Serino M, Blasco-Baque V, et al., 2017,
Gut microbiota interacts with markers of adipose tissue Browning, insulin action and plasma acetate in morbid obesity
, Molecular Nutrition and Food Research, Vol: 62, ISSN: 1613-4125SCOPE: To examine the potential relationship among gene expression markers of adipose tissue browning, gut microbiota, and insulin sensitivity in humans. METHODS AND RESULTS: Gut microbiota composition and gene markers of browning are analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue from morbidly obese subjects (n = 34). Plasma acetate is measured through 1 H NMR and insulin sensitivity using euglycemic hyperinsulinemic clamp. Subjects with insulin resistance show an increase in the relative abundance (RA) of the phyla Bacteroidetes and Proteobacteria while RA of Firmicutes is decreased. In all subjects, Firmicutes RA is negatively correlated with HbA1c and fasting triglycerides, whereas Proteobacteria RA was negatively correlated with insulin sensitivity. Firmicutes RA is positively associated with markers of brown adipocytes (PRDM16, UCP1, and DIO2) in SAT, but not in VAT. Multivariate regression analysis indicates that Firmicutes RA contributes significantly to SAT PRDM16, UCP1, and DIO2 mRNA variance after controlling for age, BMI, HbA1c , or insulin sensitivity. Interestingly, Firmicutes RA, specifically those bacteria belonging to the Ruminococcaceae family, is positively associated with plasma acetate levels, which are also linked to SAT PRDM16 mRNA and insulin sensitivity. CONCLUSION: Gut microbiota composition is linked to adipose tissue browning and insulin action in morbidly obese subjects, possibly through circulating acetate.
-
Journal articleCuthbertson L, Craven V, Bingle L, et al., 2017,
The impact of persistent bacterial bronchitis on the pulmonary microbiome of children.
, PLoS ONE, Vol: 12, ISSN: 1932-6203INTRODUCTION: Persistent bacterial bronchitis (PBB) is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of PBB. Blind, protected brushings were obtained from 20 healthy controls and 24 children with PBB, with an additional directed sample obtained from PBB patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing. RESULTS: No significant difference in bacterial diversity or community composition (R2 = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R2 = 0.08, P = 0.004) was observed among controls, in comparison with patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture. CONCLUSION: The bacteria present in the lungs of patients with PBB were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.
-
Journal articleMoffatt MF, Cookson WOCM, 2017,
The lung microbiome in health and disease
, Clinical Medicine, Vol: 17, Pages: 525-529, ISSN: 1470-2118The Human Microbiome Project began 10 years ago, leadingto a signifi cant growth in understanding of the role the humanmicrobiome plays in health and disease. In this article, weexplain with an emphasis on the lung, the origins of microbiomeresearch. We discuss how 16S rRNA gene sequencingbecame the fi rst major molecular tool to examine the bacterialcommunities present within the human body. We highlightthe pitfalls of molecular-based studies, such as false fi ndingsresulting from contamination, and the limitations of 16S rRNAgene sequencing. Knowledge about the lung microbiome hasevolved from initial scepticism to the realisation that it mighthave a signifi cant infl uence on many illnesses. We also discussthe lung microbiome in the context of disease by givingexamples of important respiratory conditions. In addition, wedraw attention to the challenges for metagenomic studies ofrespiratory samples and the importance of systematic bacterialisolation to enable host–microbiome interactions to beunderstood. We conclude by discussing how knowledge of thelung microbiome impacts current clinical diagnostics.
-
Journal articleCookson WOCM, Cox MJ, Moffatt MF, 2017,
New opportunities for managing acute and chronic lung infections.
, Nature Reviews Microbiology, Vol: 16, Pages: 111-120, ISSN: 1740-1526Lung 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 articleMoffatt MF, Cullinan P, James PL, et al., 2017,
Metal worker’s lung; spatial association with Mycobacterium avium
, Thorax, Vol: 73, Pages: 151-156, ISSN: 1468-3296Background Outbreaks of hypersensitivity pneumonitis(HP) are not uncommon in workplaces where metalworking fluid (MWF) is used to facilitate metal turning.Inhalation of microbe-contaminated MWF has beenassumed to be the cause, but previous investigationshave failed to establish a spatial relationship between acontaminated source and an outbreak.Objectives After an outbreak of five cases of HP ina UK factory, we carried out blinded, molecular-basedmicrobiological investigation of MWF samples in orderto identify potential links between specific microbial taxaand machines in the outbreak zone.Methods Custom-quantitative PCR assays, microscopyand phylogenetic analyses were performed on blindedMWF samples to quantify microbial burden and identifypotential aetiological agents of HP in metal workers.Measurements and main results MWF frommachines fed by a central sump, but not those with anisolated supply, was contaminated by mycobacteria. Thefactory sump and a single linked machine at the centre ofthe outbreak zone, known to be the workstation of theindex cases, had very high levels of detectable organisms.Phylogenetic placement of mycobacterial taxonomicmarker genes generated from these samples indicatedthat the contaminating organisms were closely related toMycobacterium avium.Conclusions We describe, for the first time, a closespatial relationship between the abundance of amycobacterium-like organism, most probably M. avium,and a localised outbreak of MWF-associated HP.The further development of sequence-based analytictechniques should assist in the prevention of thisimportant occupational disease.
-
Journal articleDumas M, Rothwell AR, Hoyles L, et al., 2017,
Microbial-host co-metabolites are prodromal markers predicting phenotypic heterogeneity in behavior, obesity and impaired glucose tolerance
, Cell Reports, Vol: 20, Pages: 136-148, ISSN: 2211-1247The influence of the gut microbiome on metabolic and behavioral traits is now widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine 1H NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n=50) and show that microbial-host co-metabolites are prodromal (i.e., early) markers predicting future divergence in metabolic (obesity and glucose homeostasis) and behaviorial (anxiety and activity) outcomes with 94-100% accuracy. Some of these metabolites also modulate disease phenotypes, best illustrated by trimethylamine-N-oxide (TMAO), a product of microbial-host co-metabolism predicting future obesity, impaired glucose tolerance (IGT) and behavior, whilst reducing endoplasmic reticulum stress and lipogenesis in 3T3-L1 adipocytes. Chronic in vivo TMAO treatment limits IGT in HFD-fed mice and isolated pancreatic islets by increasing insulin secretion. We highlight the prodromal potential of microbial metabolites to predict disease outcomes and their potential in shaping mammalian phenotypic heterogeneity.
-
Journal articleMolyneaux PL, Willis Owen SA, Cox MJ, et al., 2017,
Host-microbial interactions in idiopathic pulmonary fibrosis
, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1640-1650, ISSN: 1535-4970RATIONALE: 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.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.