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Journal articleMolyneaux PL, Cox MJ, Wells AU, et al., 2017,
Changes in the respiratory microbiome during acute exacerbations of idiopathic pulmonary fibrosis
, Respiratory Research, Vol: 18, ISSN: 1465-9921Acute 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.
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Journal articleChilloux J, Dumas ME, 2017,
Are gut microbes responsible for post-dieting weight rebound?
, Cell Metabolism, Vol: 25, Pages: 6-7, ISSN: 1932-7420One of the dieting conundrums in the age of the obesity epidemic is the cycle of weight loss and regain known as the "yo-yo effect." Thaiss et al. (2016) demonstrate that the microbiome plays a key role in this phenomenon and that simple dietary supplementations can reset the weight-rebound clock.
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Journal articleDepner M, Ege MJ, Cox MJ, et al., 2016,
Bacterial microbiota of the upper respiratory tract and childhood asthma
, Journal of Allergy and Clinical Immunology, ISSN: 1097-6825BACKGROUND: 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.
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Journal articleChilloux J, Neves AL, Boulangé CL, et al., 2016,
The microbial-mammalian metabolic axis: a critical symbiotic relationship
, Current Opinion in Clinical Nutrition and Metabolic Care, Vol: 19, Pages: 250-256, ISSN: 1473-6519Purpose of review: The microbial-mammalian symbiosis plays a critical role in metabolic health. Microbial metabolites emerge as key messengers in the complex communication between the gut microbiota and their host. These chemical signals are mainly derived from nutritional precursors, which in turn are also able to modify gut microbiota population. Recent advances in the characterization of the gut microbiome and the mechanisms involved in this symbiosis allow the development of nutritional interventions. This review covers the latest findings on the microbial-mammalian metabolic axis as a critical symbiotic relationship particularly relevant to clinical nutrition.Recent findings: The modulation of host metabolism by metabolites derived from the gut microbiota highlights the importance of gut microbiota in disease prevention and causation. The composition of microbial populations in our gut ecosystem is a critical pathophysiological factor, mainly regulated by diet, but also by the host's characteristics (e.g. genetics, circadian clock, immune system, age). Tailored interventions, including dietary changes, the use of antibiotics, prebiotic and probiotic supplementation and faecal transplantation are promising strategies to manipulate microbial ecology.Summary: The microbiome is now considered as an easily reachable target to prevent and treat related diseases. Recent findings in both mechanisms of its interactions with host metabolism and in strategies to modify gut microbiota will allow us to develop more effective treatments especially in metabolic diseases.
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Journal articleBoulangé CL, Neves AL, Chilloux J, et al., 2016,
Impact of the gut microbiota on inflammation, obesity, and metabolic disease
, Genome Medicine, Vol: 8, ISSN: 1756-994XThe human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gut microbiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gut microbiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gut microbiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.
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Journal articleZhang Q, Cox M, Liang Z, et al., 2016,
Airway microbiota in severe asthma and relationship to asthma severity and phenotypes
, PLOS One, Vol: 11, ISSN: 1932-6203Background: 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.
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Journal articleDumas M-E, 2016,
Is the way we're dieting wrong?
, Genome Medicine, Vol: 8, ISSN: 1756-994XProgress in personalized medicine is now beingtranslated to personalized nutrition. A recent proofof-conceptstudy shows that the increase in bloodglucose levels after a meal is highly variable betweenindividuals, but can be predicted by using acomputational model that combines information fromgut microbiome profiles and dietary questionnaires.This study raises questions about the usefulness ofuniversal diet recommendations, and suggests wemight need to move on to personalized diets.
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Journal articleNeves AL, Chilloux J, Sarafian MH, et al., 2015,
The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases
, Current Opinion in Pharmacology, Vol: 25, Pages: 36-44, ISSN: 1471-4892Consisting of trillions of non-pathogenic bacteria living in a symbiotic relationship with their mammalian host, the gut microbiota has emerged in the past decades as one of the key drivers for cardiometabolic diseases (CMD). By degrading dietary substrates, the gut microbiota produces several metabolites that bind human pharmacological targets, impact subsequent signalling networks and in fine modulate host's metabolism. In this review, we revisit the pharmacological relevance of four classes of gut microbial metabolites in CMD: short-chain fatty acids (SCFA), bile acids, methylamines and indoles. Unravelling the signalling mechanisms of the microbial–mammalian metabolic axis adds one more layer of complexity to the physiopathology of CMD and opens new avenues for the development of microbiota-based pharmacological therapies.
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Journal articleSarafian MH, Lewis MR, Pechlivanis A, et al., 2015,
Bile Acid Profiling and Quantification in Biofluids Using Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry
, Analytical Chemistry, Vol: 87, Pages: 9662-9670, ISSN: 1520-6882Bile acids are important end products of cholesterol metabolism. While they have been identified as key factors in lipid emulsification and absorption due to their detergent properties, bile acids have also been shown to act as signaling molecules and intermediates between the host and the gut microbiota. To further the investigation of bile acid functions in humans, an advanced platform for high throughput analysis is essential. Herein, we describe the development and application of a 15 min UPLC procedure for the separation of bile acid species from human biofluid samples requiring minimal sample preparation. High resolution time-of-flight mass spectrometry was applied for profiling applications, elucidating rich bile acid profiles in both normal and disease state plasma. In parallel, a second mode of detection was developed utilizing tandem mass spectrometry for sensitive and quantitative targeted analysis of 145 bile acid (BA) species including primary, secondary, and tertiary bile acids. The latter system was validated by testing the linearity (lower limit of quantification, LLOQ, 0.25–10 nM and upper limit of quantification, ULOQ, 2.5–5 μM), precision (≈6.5%), and accuracy (81.2–118.9%) on inter- and intraday analysis achieving good recovery of bile acids (serum/plasma 88% and urine 93%). The ultra performance liquid chromatography–mass spectrometry (UPLC-MS)/MS targeted method was successfully applied to plasma, serum, and urine samples in order to compare the bile acid pool compositional difference between preprandial and postprandial states, demonstrating the utility of such analysis on human biofluids.
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Journal articleCox 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
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