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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 -
Journal articleShoaie S, Ghaffari P, Kovatcheva-Datchary P, et al., 2015,
Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome
, Cell Metabolism, Vol: 22, Pages: 320-331, ISSN: 1932-7420The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.
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Journal articleBrill S, Law M, El-Emir E, et al., 2015,
Effects of different antibiotic classes on airwaybacteria in stable COPD using culture and molecularQ1 techniques: a randomised controlled trial
, Thorax, Vol: 70, Pages: 930-938, ISSN: 1468-3296BackgroundLong term antibiotic therapy is used to prevent exacerbations of chronic obstructive pulmonary disease (COPD) but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo. MethodsThis was a single-centre, single-blind, randomised placebo-controlled trial (clinicaltrials.gov number NCT01398072). Patients ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400mg daily for 5 days/4 weeks, doxycycline 100mg/day, azithromycin 250mg 3x/week or one placebo tablet daily for 13 weeks. The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S qPCR, sputum inflammation and antibiotic resistance. Results99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed. After adjustment, there was a mean reduction in bacterial load of 0.42 log10 cfu/ml (95% CI -0.08, 0.91, p=0.10) with moxifloxacin, 0.11 (-0.33, 0.55, p=0.62) with doxycycline, and 0.08 (-0.38, 0.54, p=0.73) with azithromycin from placebo, respectively. There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation. More treatment-related adverse events occurred with moxifloxacin. Of note, mean inhibitory concentrations of cultured isolates increased by at least 3 times over placebo in all treatment arms.ConclusionsTotal airway bacterial load did not decrease significantly after three months of antibiotic therapy. Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.
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Journal articleShaw AG, Sim K, Randell P, et al., 2015,
Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants
, PLOS One, Vol: 10, ISSN: 1932-6203
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