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Featured researches published by Edi Prifti.


Nature | 2013

Richness of human gut microbiome correlates with metabolic markers

Trine Nielsen; Junjie Qin; Edi Prifti; Falk Hildebrand; Gwen Falony; Mathieu Almeida; Manimozhiyan Arumugam; Jean-Michel Batto; Sean Kennedy; Pierre Leonard; Junhua Li; Kristoffer Sølvsten Burgdorf; Niels Grarup; Torben Jørgensen; Ivan Brandslund; Henrik Bjørn Nielsen; Agnieszka Sierakowska Juncker; Marcelo Bertalan; Florence Levenez; Nicolas Pons; Simon Rasmussen; Shinichi Sunagawa; Julien Tap; Sebastian Tims; Erwin G. Zoetendal; Søren Brunak; Karine Clément; Joël Doré; Michiel Kleerebezem; Karsten Kristiansen

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.


Nature | 2013

Dietary intervention impact on gut microbial gene richness.

Aurélie Cotillard; Sean Kennedy; Ling Chun Kong; Edi Prifti; Nicolas Pons; Mathieu Almeida; Benoit Quinquis; Florence Levenez; Nathalie Galleron; Sophie Gougis; Salwa Rizkalla; Jean-Michel Batto; Pierre Renault; Joël Doré; Jean-Daniel Zucker; Karine Clément; S D Ehrlich

Complex gene–environment interactions are considered important in the development of obesity. The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial populations. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches, which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes, but the analyses were carried out mainly in non-intervention settings. To investigate the temporal relationships between food intake, gut microbiota and metabolic and inflammatory phenotypes, we conducted diet-induced weight-loss and weight-stabilization interventions in a study sample of 38 obese and 11 overweight individuals. Here we report that individuals with reduced microbial gene richness (40%) present more pronounced dys-metabolism and low-grade inflammation, as observed concomitantly in the accompanying paper. Dietary intervention improves low gene richness and clinical phenotypes, but seems to be less efficient for inflammation variables in individuals with lower gene richness. Low gene richness may therefore have predictive potential for the efficacy of intervention.


Nature Biotechnology | 2014

An integrated catalog of reference genes in the human gut microbiome

Junhua Li; Huijue Jia; Xianghang Cai; Huanzi Zhong; Qiang Feng; Shinichi Sunagawa; Manimozhiyan Arumugam; Jens Roat Kultima; Edi Prifti; Trine Nielsen; Agnieszka Sierakowska Juncker; Chaysavanh Manichanh; Bing Chen; Wenwei Zhang; Florence Levenez; Juan Wang; Xun Xu; Liang Xiao; Suisha Liang; Dongya Zhang; Zhaoxi Zhang; Weineng Chen; Hailong Zhao; Jumana Y. Al-Aama; Sherif Edris; Huanming Yang; Jian Wang; Torben Hansen; Henrik Bjørn Nielsen; Søren Brunak

Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease.


Nature | 2015

Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

Kristoffer Forslund; Falk Hildebrand; Trine Nielsen; Gwen Falony; Shinichi Sunagawa; Edi Prifti; Sara Vieira-Silva; Valborg Gudmundsdottir; Helle Krogh Pedersen; Manimozhiyan Arumugam; Karsten Kristiansen; Anita Yvonne Voigt; Henrik Vestergaard; Rajna Hercog; Paul Igor Costea; Jens Roat Kultima; Junhua Li; Torben Jørgensen; Florence Levenez; Joël Doré; H. Bjørn Nielsen; Søren Brunak; Jeroen Raes; Torben Hansen; Jun Wang; S. Dusko Ehrlich; Peer Bork; Oluf Pedersen

Citing this paper Please note that where the full-text provided on Kings Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publishers definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publishers website for any subsequent corrections.In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.


Nature Biotechnology | 2014

Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes.

H. Bjørn Nielsen; Mathieu Almeida; Agnieszka Sierakowska Juncker; Simon Rasmussen; Junhua Li; Shinichi Sunagawa; Damian Rafal Plichta; Laurent Gautier; Anders Gorm Pedersen; Eric Pelletier; Ida Bonde; Trine Nielsen; Chaysavanh Manichanh; Manimozhiyan Arumugam; Jean-Michel Batto; Marcelo B Quintanilha dos Santos; Nikolaj Blom; Natalia Borruel; Kristoffer Sølvsten Burgdorf; Fouad Boumezbeur; Francesc Casellas; Joël Doré; Piotr Dworzynski; Francisco Guarner; Torben Hansen; Falk Hildebrand; Rolf Sommer Kaas; Sean Kennedy; Karsten Kristiansen; Jens Roat Kultima

Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.


Nature | 2016

Human gut microbes impact host serum metabolome and insulin sensitivity

Helle Krogh Pedersen; Valborg Gudmundsdottir; Henrik Bjørn Nielsen; Tuulia Hyötyläinen; Trine Nielsen; Benjamin Anderschou Holbech Jensen; Kristoffer Forslund; Falk Hildebrand; Edi Prifti; Gwen Falony; Florence Levenez; Joël Doré; Ismo Mattila; Damian Rafal Plichta; Päivi Pöhö; Lars Hellgren; Manimozhiyan Arumugam; Shinichi Sunagawa; Sara Vieira-Silva; Torben Jørgensen; Jacob Holm; Kajetan Trošt; Karsten Kristiansen; Susanne Brix; Jeroen Raes; Jun Wang; Torben Hansen; Peer Bork; Søren Brunak; Matej Orešič

Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.


The American Journal of Clinical Nutrition | 2012

Differential effects of macronutrient content in 2 energy-restricted diets on cardiovascular risk factors and adipose tissue cell size in moderately obese individuals: a randomized controlled trial

Salwa Rizkalla; Edi Prifti; Aurélie Cotillard; Véronique Pelloux; Christine Rouault; Reginald Allouche; Muriel Laromiguiere; Ling-Chun Kong; Froogh Darakhshan; Florence Massiera; Karine Clément

BACKGROUND The most effective and safe dietary approach for weight loss and its impact on the metabolic functions and morphology of adipose tissue remain unclear. OBJECTIVES We evaluated whether an energy-restricted high-protein diet with a low glycemic index and soluble fiber (LC-P-LGI) would be more effective than a low-calorie conventional diet (LC-CONV) on weight loss and related metabolic risk factors. We further determined factors that may influence adipocyte size during energy restriction. DESIGN Thirteen obese participants were randomly assigned in a crossover design to 2 periods of a 4-wk hypocaloric diet as either LC-P-LGI or LC-CONV, separated by 8-wk washout intervals. RESULTS In comparison with the LC-CONV diet, the main effect of the LC-P-LGI diet was a greater decrease in adipocyte diameter (P = 0.048), plasma plasminogen activator inhibitor protein-1 (P = 0.019), vascular endothelial growth factor (P = 0.032), and interferon-γ inducible protein 10 (P = 0.010). Whereas fasting plasma glucose and high-sensitivity C-reactive protein decreased only after the LC-P-LGI diet, with no differences between diets, fasting plasma insulin and insulin resistance were lower after the LC-CONV diet. The diet results did not differ for body composition and lipid variables. Kinetic modifications in adipocyte diameter were associated with metabolic variables and genes implicated in adipocyte proliferation, apoptosis, and angiogenesis. CONCLUSIONS In comparison with the LC-CONV diet, the LC-P-LGI diet was associated with improvement in some cardiometabolic risk factors and greater reduction in adipocyte size. Profiles of genes involved in inhibiting adipogenesis and angiogenesis, but increasing apoptosis, were correlated with decreased adipocyte size. This study provides insight into the adipose tissue-remodeling changes that induce regulation of adipocyte size during dietary weight loss. This trial was registered at clinicaltrials.gov as NCT01312740.


British Journal of Nutrition | 2015

Dietary modulation of the gut microbiota – a randomised controlled trial in obese postmenopausal women

Lena Kirchner Brahe; Edi Prifti; Nicolas Pons; Sean Kennedy; Trine Blædel; Janet Håkansson; Trine Kastrup Dalsgaard; Torben Hansen; Oluf Pedersen; Arne Astrup; S. Dusko Ehrlich; Lesli H. Larsen

The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of either L. paracasei F19 (9·4 × 1010 colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (P< 0·05) and improved insulin sensitivity measured by Matsuda index (P< 0·05). Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species (P< 0·01), including decreased relative abundance of eight Faecalibacterium species. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species.


Nature microbiology | 2016

A reference gene catalogue of the pig gut microbiome

Liang Xiao; Jordi Estellé; Pia Kiilerich; Yuliaxis Ramayo-Caldas; Zhongkui Xia; Qiang Feng; Suisha Liang; Anni Øyan Pedersen; Niels Jørgen Kjeldsen; Chuan Liu; Emmanuelle Maguin; Joël Doré; Nicolas Pons; Edi Prifti; Junhua Li; Huijue Jia; Xin Liu; Xun Xu; S D Ehrlich; Lise Madsen; Karsten Kristiansen; Claire Rogel-Gaillard; Jun Wang

The pig is a major species for livestock production and is also extensively used as the preferred model species for analyses of a wide range of human physiological functions and diseases1. The importance of the gut microbiota in complementing the physiology and genome of the host is now well recognized2. Knowledge of the functional interplay between the gut microbiota and host physiology in humans has been advanced by the human gut reference catalogue3,4. Thus, establishment of a comprehensive pig gut microbiome gene reference catalogue constitutes a logical continuation of the recently published pig genome5. By deep metagenome sequencing of faecal DNA from 287 pigs, we identified 7.7 million non-redundant genes representing 719 metagenomic species. Of the functional pathways found in the human catalogue, 96% are present in the pig catalogue, supporting the potential use of pigs for biomedical research. We show that sex, age and host genetics are likely to influence the pig gut microbiome. Analysis of the prevalence of antibiotic resistance genes demonstrated the effect of eliminating antibiotics from animal diets and thereby reducing the risk of spreading antibiotic resistance associated with farming systems.


Nutrition & Diabetes | 2015

Specific gut microbiota features and metabolic markers in postmenopausal women with obesity.

Lena Kirchner Brahe; Edi Prifti; Nicolas Pons; Sean Kennedy; T. Hansen; Oluf Pedersen; Arne Astrup; S D Ehrlich; Lesli H. Larsen

Background:Gut microbial gene richness and specific bacterial species are associated with metabolic risk markers in humans, but the impact of host physiology and dietary habits on the link between the gut microbiota and metabolic markers remain unclear. The objective of this study was to identify gut metagenomic markers associated with estimates of insulin resistance, lipid metabolism and inflammation in obesity, and to explore whether the associations between metagenomic and metabolic markers persisted after adjustment for body fat, age and habitual dietary intake.Methods:Faecal DNA from 53 women with obesity was analysed through quantitative metagenomic sequencing and analysis, and a systematic search was performed for bacterial genes associated with estimates of insulin resistance, inflammation and lipid metabolism. Subsequently, the correlations between metagenomic species and metabolic markers were tested by linear regression models, with and without covariate adjustment.Results:One hundred and fourteen metagenomic species correlated with metabolic markers (P<0.001) including Akkermansia muciniphila, Bilophila wadsworthia, Bifidobacterium longum and Faecalibacterium prausnitzii, but also species not previously associated with metabolic markers including Bacteroides faecis and Dorea longicatena. The majority of the identified correlations between bacterial species and metabolic markers persisted after adjustment for differences in body fat, age and dietary macronutrient composition; however, the negative correlation with insulin resistance observed for B. longum and F. prausnitzii appeared to be modified by the intake of dietary fibre and fat, respectively.Conclusions:This study shows that several gut bacterial species are linked to metabolic risk markers in obesity, also after adjustment for potential confounders, such as long-term diet composition. The study supports the use of gut metagenomic markers for metabolic disease prediction and warrants further investigation of causality.

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Joël Doré

Institut national de la recherche agronomique

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Nicolas Pons

Institut national de la recherche agronomique

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Florence Levenez

Institut national de la recherche agronomique

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S. Dusko Ehrlich

Institut national de la recherche agronomique

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Sean Kennedy

Institut national de la recherche agronomique

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Torben Hansen

University of Copenhagen

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Trine Nielsen

University of Copenhagen

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