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1. Prediction of the intestinal resistome by a three-dimensional structure-based method

Author

Ruppé, Etienne, Ghozlane, Amine, Tap, Julien, Pons, Nicolas, Alvarez, Anne-Sophie, Maziers, Nicolas, Cuesta, Trinidad, Hernando-Amado, Sara, Clares, Irene, Martínez, Jose Luís, Coque, Teresa M., Baquero, Fernando, Lanza, Val F., Máiz, Luis, Goulenok, Tiphaine, de Lastours, Victoire, Amor, Nawal, Fantin, Bruno, Wieder, Ingrid, Andremont, Antoine, van Schaik, Willem, Rogers, Malbert, Zhang, Xinglin, Willems, Rob J. L., de Brevern, Alexandre G., Batto, Jean-Michel, Blottière, Hervé M., Léonard, Pierre, Léjard, Véronique, Letur, Aline, Levenez, Florence, Weiszer, Kevin, Haimet, Florence, Doré, Joël, Kennedy, Sean P., and Ehrlich, S. Dusko

Published
2019
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2. Alterations of the human gut microbiome in liver cirrhosis

Author

Qin, Nan, Yang, Fengling, Li, Ang, Prifti, Edi, Chen, Yanfei, Shao, Li, Guo, Jing, Le Chatelier, Emmanuelle, Yao, Jian, Wu, Lingjiao, Zhou, Jiawei, Ni, Shujun, Liu, Lin, Pons, Nicolas, Batto, Jean Michel, Kennedy, Sean P., Leonard, Pierre, Yuan, Chunhui, Ding, Wenchao, Chen, Yuanting, Hu, Xinjun, Zheng, Beiwen, Qian, Guirong, Xu, Wei, Ehrlich, S. Dusko, Zheng, Shusen, and Li, Lanjuan

Subjects
Physiological aspects, Research, Microbiota (Symbiotic organisms) -- Physiological aspects, Medical research, Liver cirrhosis -- Research, Medicine, Experimental
Abstract

Cirrhosis is an advanced liver disease resulting from acute or chronic liver injury, including alcohol abuse, obesity and hepatitis virus infection. The prognosis for patients with decompensated liver cirrhosis is [...], Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched inpatients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

Published
2014
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3. Dietary intervention impact on gut microbial gene richness

Author

Cotillard, Aurelie, Kennedy, Sean P., Kong, Ling Chun, Prifti, Edi, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Levenez, Florence, Galleron, Nathalie, Gougis, Sophie, Rizkalla, Salwa, Batto, Jean-Michel, Renault, Pierre, Dore, Joel, Zucker, Jean-Daniel, Clement, Karine, and Ehrlich, Stanislav Dusko

Subjects
Genetic aspects, Microbiota (Symbiotic organisms) -- Genetic aspects
Abstract

Complex gene-environment interactions are considered important in the development of obesity (1). The composition of the gut microbiota can determine the efficacy of energy harvest from food (2-4) and changes [...]

Published
2013

4. Richness of human gut microbiome correlates with metabolic markers

Author

Le Chatelier, Emmanuelle, Nielsen, Trine, Qin, Junjie, Prifti, Edi, Hildebrand, Falk, Falony, Gwen, Almeida, Mathieu, Arumugam, Manimozhiyan, Batto, Jean-Michel, Kennedy, Sean, Leonard, Pierre, Li, Junhua, Burgdorf, Kristoffer, Grarup, Niels, Jørgensen, Torben, Brandslund, Ivan, Nielsen, Henrik Bjørn, Juncker, Agnieszka S., Bertalan, Marcelo, Levenez, Florence, Pons, Nicolas, Rasmussen, Simon, Sunagawa, Shinichi, Tap, Julien, Tims, Sebastian, Zoetendal, Erwin G., Brunak, Søren, Clément, Karine, Doré, Joël, Kleerebezem, Michiel, Kristiansen, Karsten, Renault, Pierre, Sicheritz-Ponten, Thomas, de Vos, Willem M., Zucker, Jean-Daniel, Raes, Jeroen, Hansen, Torben, Bork, Peer, Wang, Jun, Ehrlich, S. Dusko, and Pedersen, Oluf

Published
2013
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5. A metagenome-wide association study of gut microbiota in type 2 diabetes

Author

Qin, Junjie, Li, Yingrui, Cai, Zhiming, Li, Shenghui, Zhu, Jianfeng, Zhang, Fan, Liang, Suisha, Zhang, Wenwei, Guan, Yuanlin, Shen, Dongqian, Peng, Yangqing, Zhang, Dongya, Jie, Zhuye, Wu, Wenxian, Qin, Youwen, Xue, Wenbin, Li, Junhua, Han, Lingchuan, Lu, Donghui, Wu, Peixian, Dai, Yali, Sun, Xiaojuan, Li, Zesong, Tang, Aifa, Zhong, Shilong, Li, Xiaoping, Chen, Weineng, Xu, Ran, Wang, Mingbang, Feng, Qiang, Gong, Meihua, Yu, Jing, Zhang, Yanyan, Zhang, Ming, Hansen, Torben, Sanchez, Gaston, Raes, Jeroen, Falony, Gwen, Okuda, Shujiro, Almeida, Mathieu, LeChatelier, Emmanuelle, Renault, Pierre, Pons, Nicolas, Batto, Jean-Michel, Zhang, Zhaoxi, Chen, Hua, Yang, Ruifu, Zheng, Weimou, Li, Songgang, Yang, Huanming, Wang, Jian, Ehrlich, Dusko S., Nielsen, Rasmus, Pedersen, Oluf, Kristiansen, Karsten, and Wang, Jun

Published
2012
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6. Enterotypes of the human gut microbiome

Author

Arumugam, Manimozhiyan, Raes, Jeroen, Pelletier, Eric, Le Paslier, Denis, Yamada, Takuji, Mende, Daniel R., Fernandes, Gabriel R., Tap, Julien, Bruls, Thomas, Batto, Jean-Michel, Bertalan, Marcelo, Borruel, Natalia, Casellas, Francesc, Fernandez, Leyden, Gautier, Laurent, Hansen, Torben, Hattori, Masahira, Hayashi, Tetsuya, Kleerebezem, Michiel, Kurokawa, Ken, Leclerc, Marion, Levenez, Florence, Manichanh, Chaysavanh, Nielsen, Bjørn H., Nielsen, Trine, Pons, Nicolas, Poulain, Julie, Qin, Junjie, Sicheritz-Ponten, Thomas, Tims, Sebastian, Torrents, David, Ugarte, Edgardo, Zoetendal, Erwin G., Wang, Jun, Guarner, Francisco, Pedersen, Oluf, de Vos, Willem M., Brunak, Søren, Doré, Joel, Antolín, María, Artiguenave, François, Blottiere, Hervé M., Almeida, Mathieu, Brechot, Christian, Cara, Carlos, Chervaux, Christian, Cultrone, Antonella, Delorme, Christine, Denariaz, Gérard, Dervyn, Rozenn, Foerstner, Konrad U., Friss, Carsten, van de Guchte, Maarten, Guedon, Eric, Haimet, Florence, Huber, Wolfgang, van Hylckama-Vlieg, Johan, Jamet, Alexandre, Juste, Catherine, Kaci, Ghalia, Knol, Jan, Lakhdari, Omar, Layec, Severine, Le Roux, Karine, Maguin, Emmanuelle, Mérieux, Alexandre, Melo Minardi, Raquel, Mʼrini, Christine, Muller, Jean, Oozeer, Raish, Parkhill, Julian, Renault, Pierre, Rescigno, Maria, Sanchez, Nicolas, Sunagawa, Shinichi, Torrejon, Antonio, Turner, Keith, Vandemeulebrouck, Gaetana, Varela, Encarna, Winogradsky, Yohanan, Zeller, Georg, Weissenbach, Jean, Ehrlich, S. Dusko, and Bork, Peer

Published
2011
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7. A human gut microbial gene catalogue established by metagenomic sequencing

Author

Qin, Junjie, Li, Ruiqiang, Raes, Jeroen, Arumugam, Manimozhiyan, Burgdorf, Kristoffer Solvsten, Manichanh, Chaysavanh, Nielsen, Trine, Pons, Nicolas, Levenez, Florence, Yamada, Takuji, Mende, Daniel R., Li, Junhua, Xu, Junming, Li, Shaochuan, Li, Dongfang, Cao, Jianjun, Wang, Bo, Liang, Huiqing, Zheng, Huisong, Xie, Yinlong, Tap, Julien, Lepage, Patricia, Bertalan, Marcelo, Batto, Jean-Michel, Hansen, Torben, Le Paslier, Denis, Linneberg, Allan, Nielsen, Bjørn H., Pelletier, Eric, Renault, Pierre, Sicheritz-Ponten, Thomas, Turner, Keith, Zhu, Hongmei, Yu, Chang, Li, Shengting, Jian, Min, Zhou, Yan, Li, Yingrui, Zhang, Xiuqing, Li, Songgang, Qin, Nan, Yang, Huanming, Wang, Jian, Brunak, Søren, Doré, Joel, Guarner, Francisco, Kristiansen, Karsten, Pedersen, Oluf, Parkhill, Julian, Weissenbach, Jean, Antolin, Maria, Artiguenave, François, Blottiere, Hervé, Borruel, Natalia, Bruls, Thomas, Casellas, Francesc, Chervaux, Christian, Cultrone, Antonella, Delorme, Christine, Denariaz, Gérard, Dervyn, Rozenn, Forte, Miguel, Friss, Carsten, van de Guchte, Maarten, Guedon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kaci, Ghalia, Kleerebezem, Michiel, Knol, Jan, Kristensen, Michel, Layec, Severine, Le Roux, Karine, Leclerc, Marion, Maguin, Emmanuelle, Minardi, Raquel Melo, Oozeer, Raish, Rescigno, Maria, Sanchez, Nicolas, Tims, Sebastian, Torrejon, Toni, Varela, Encarna, de Vos, Willem, Winogradsky, Yohanan, Zoetendal, Erwin, Bork, Peer, Ehrlich, Dusko S., and Wang, Jun

Published
2010
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8. Prediction of the intestinal resistome by a three-dimensional structure-based method

Author

MMB Moleculair A, Infection & Immunity, Ruppé, Etienne, Ghozlane, Amine, Tap, Julien, Pons, Nicolas, Alvarez, Anne Sophie, Maziers, Nicolas, Cuesta, Trinidad, Hernando-Amado, Sara, Clares, Irene, Martínez, Jose Luís, Coque, Teresa M., Baquero, Fernando, Lanza, Val F., Máiz, Luis, Goulenok, Tiphaine, de Lastours, Victoire, Amor, Nawal, Fantin, Bruno, Wieder, Ingrid, Andremont, Antoine, van Schaik, Willem, Rogers, Malbert, Zhang, Xinglin, Willems, Rob J.L., de Brevern, Alexandre G., Batto, Jean Michel, Blottière, Hervé M., Léonard, Pierre, Léjard, Véronique, Letur, Aline, Levenez, Florence, Weiszer, Kevin, Haimet, Florence, Doré, Joël, Kennedy, Sean P., Ehrlich, S. Dusko, MMB Moleculair A, Infection & Immunity, Ruppé, Etienne, Ghozlane, Amine, Tap, Julien, Pons, Nicolas, Alvarez, Anne Sophie, Maziers, Nicolas, Cuesta, Trinidad, Hernando-Amado, Sara, Clares, Irene, Martínez, Jose Luís, Coque, Teresa M., Baquero, Fernando, Lanza, Val F., Máiz, Luis, Goulenok, Tiphaine, de Lastours, Victoire, Amor, Nawal, Fantin, Bruno, Wieder, Ingrid, Andremont, Antoine, van Schaik, Willem, Rogers, Malbert, Zhang, Xinglin, Willems, Rob J.L., de Brevern, Alexandre G., Batto, Jean Michel, Blottière, Hervé M., Léonard, Pierre, Léjard, Véronique, Letur, Aline, Levenez, Florence, Weiszer, Kevin, Haimet, Florence, Doré, Joël, Kennedy, Sean P., and Ehrlich, S. Dusko

Published
2019

9. Prediction of the intestinal resistome by a three-dimensional structure-based method

Author

European Commission, Instituto de Salud Carlos III, Comunidad de Madrid, European Society of Clinical Microbiology and Infectious Diseases, Ruppé, Etienne, Ghozlane, Amine, Tap, Julien, Pons, Nicolás, Álvarez, Anne-Sophie, Maziers, Nicolás, Cuesta, Trinidad, Hernando-Amado, Sara, Clares, Irene, Martínez, José Luis, Coque, Teresa M., Baquero, Fernando, Lanza, Val F., Máiz, Luis, Goulenok, Tiphaine, Lastours, Victoire de, Amor, Nawal, Fantin, Bruno, Wieder, Ingrid, Andremont, Antoine, Schaik, Willem van, Rogers, Malbert, Zhang, Xinglin, Willems, Rob J., Brevern, Alexandre G. de, Batto, Jean-Michel, Blottière, Hervé M., Léonard, Pierre, Léjard, Véronique, Letur, Aline, Levenez, Florence, Weiszer, Kevin, Haimet, Florence, Doré, Joël, Kennedy, Sean, Ehrlich, S. Dusko, European Commission, Instituto de Salud Carlos III, Comunidad de Madrid, European Society of Clinical Microbiology and Infectious Diseases, Ruppé, Etienne, Ghozlane, Amine, Tap, Julien, Pons, Nicolás, Álvarez, Anne-Sophie, Maziers, Nicolás, Cuesta, Trinidad, Hernando-Amado, Sara, Clares, Irene, Martínez, José Luis, Coque, Teresa M., Baquero, Fernando, Lanza, Val F., Máiz, Luis, Goulenok, Tiphaine, Lastours, Victoire de, Amor, Nawal, Fantin, Bruno, Wieder, Ingrid, Andremont, Antoine, Schaik, Willem van, Rogers, Malbert, Zhang, Xinglin, Willems, Rob J., Brevern, Alexandre G. de, Batto, Jean-Michel, Blottière, Hervé M., Léonard, Pierre, Léjard, Véronique, Letur, Aline, Levenez, Florence, Weiszer, Kevin, Haimet, Florence, Doré, Joël, Kennedy, Sean, and Ehrlich, S. Dusko

Abstract

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens via mobile genetic elements. Yet, this assumption is poorly supported by empirical evidence due to the distant homologies between known ARDs (mostly from culturable bacteria) and ARDs from the intestinal microbiota. Consequently, an accurate census of intestinal ARDs (that is, the intestinal resistome) has not yet been fully determined. For this purpose, we developed and validated an annotation method (called pairwise comparative modelling) on the basis of a three-dimensional structure (homology comparative modelling), leading to the prediction of 6,095 ARDs in a catalogue of 3.9 million proteins from the human intestinal microbiota. We found that the majority of predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino acid identity 29.8%) and found little evidence supporting their transfer between species. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n = 663) into six resistotypes that were connected to the previously described enterotypes. Finally, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results indicate that the majority of intestinal microbiota ARDs can be considered intrinsic to the dominant commensal microbiota and that these genes are rarely shared with bacterial pathogens.

Published
2019

10. An integrated catalog of reference genes in the human gut microbiome

Author

Li, Junhua, Jia, Huijue, Cai, Xianghang, Zhong, Huanzi, Feng, Qiang, Sunagawa, Shinichi, Arumugam, Manimozhiyan, Kultima, Jens Roat, Prifti, Edi, Nielsen, Trine, Juncker, Agnieszka Sierakowska, Manichanh, Chaysavanh, Chen, Bing, Zhang, Wenwei, Levenez, Florence, Wang, Juan, Xu, Xun, Xiao, Liang, Liang, Suisha, Zhang, Dongya, Zhang, Zhaoxi, Chen, Weineng, Zhao, Hailong, Al-Aama, Jumana Yousuf, Edris, Sherif, Yang, Huanming, Wang, Jian, Hansen, Torben, Nielsen, Henrik Bjørn, Brunak, Søren, Kristiansen, Karsten, Guarner, Francisco, Pedersen, Oluf, Dore, Joel, Ehrlich, Stanislav, Bork, Peer, Wang, Jun, Pons, Nicolas, Le Chatelier, Emmanuelle, Batto, Jean-Michel, Kennedy, Sean, Haimet, Florence, Winogradsky, Yohanan, Cultrone, Antonietta, Leclerc, Marion, Juste, Catherine, Guedon, Eric, Delorme, Christine, Layec, Séverine, Kaci, Ghalia, Van De Guchte, Maarten, Vandemeulebrouck, Gaetana, Jamet, Alexandre, Dervyn, Rozenn, Sanchez, Nicolas, Blottiere, Herve, Maguin, Emmanuelle, Renault, Pierre, Tap, Julien, BGI Shenzhen, School of Bioscience and Biotechnology, Southern University of Science and Technology [Shenzhen] (SUSTech), Department of Biology [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), European Molecular Biology Laboratory, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Center for Biological Sequence Analysis, Technical University of Denmark [Lyngby] (DTU), Digestive System Research Unit, Vall d'Hebron University Hospital [Barcelona], Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Princess Al-Jawhara AlBrahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, Department of Biological Sciences, Faculty of Science, Princess Al-Jawhara AlBrahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), James D. Watson Institute of Genome Science, Zhejiang University, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre for Host-Microbiome Interactions, Dental Institute Central Office, King‘s College London, Max Delbrück Center for Molecular Medicine, Macau University of Science and Technology (MUST), Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA), Beijing Genomics Institute [Shenzhen] (BGI), MetaGenoPolis, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), and Helmholtz-Gemeinschaft = Helmholtz Association

Subjects
[SDV]Life Sciences [q-bio], reference genes, Applied Microbiology and Biotechnology, Genome, Human health, Microbiologie, Reference genes, population-size, health care economics and organizations, Genetics, 0303 health sciences, Microbiota, alignment, tool, twins, Intestines, impact, Molecular Medicine, Biotechnology, information science, Biomedical Engineering, Bioengineering, danish individual, Computational biology, Biology, Microbiology, metagenome, 03 medical and health sciences, Human gut, Catalogs as Topic, Humans, natural sciences, Host-Microbe Interactomics, Microbiome, Gene, VLAG, 030304 developmental biology, human gut microbiome, fecal microbiota, 030306 microbiology, eukaryotic diversity, metagenomic of the human intestinal tract, country specific gut microbial signature, Metagenomics, WIAS, sequences, genomes, chinese individual, Human Microbiome Project
Abstract

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.

Published
2014
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11. Prediction of the intestinal resistome by a three-dimensional structure-based method

Author

Ruppé, Etienne, primary, Ghozlane, Amine, additional, Tap, Julien, additional, Pons, Nicolas, additional, Alvarez, Anne-Sophie, additional, Maziers, Nicolas, additional, Cuesta, Trinidad, additional, Hernando-Amado, Sara, additional, Clares, Irene, additional, Martínez, Jose Luís, additional, Coque, Teresa M., additional, Baquero, Fernando, additional, Lanza, Val F., additional, Máiz, Luis, additional, Goulenok, Tiphaine, additional, de Lastours, Victoire, additional, Amor, Nawal, additional, Fantin, Bruno, additional, Wieder, Ingrid, additional, Andremont, Antoine, additional, van Schaik, Willem, additional, Rogers, Malbert, additional, Zhang, Xinglin, additional, Willems, Rob J. L., additional, de Brevern, Alexandre G., additional, Batto, Jean-Michel, additional, Blottière, Hervé M., additional, Léonard, Pierre, additional, Léjard, Véronique, additional, Letur, Aline, additional, Levenez, Florence, additional, Weiszer, Kevin, additional, Haimet, Florence, additional, Doré, Joël, additional, Kennedy, Sean P., additional, and Ehrlich, S. Dusko, additional

Published
2018
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12. Transcriptional interactions suggest niche segregation among microorganisms in the human gut

Author

Plichta, Damian Rafal, Juncker, Agnieszka Sierakowska, Bertalan, Marcelo, Rettedal, Elizabeth, Gautier, Laurent, Varela, Encarna, Manichanh, Chaysavanh, Fouqueray, Charlène, Levenez, Florence, Nielsen, Trine, Dore, Joel, Machado, Ana Manuel Dantas, de Evgrafov, Mari Cristina Rodriguez, Hansen, Torben, Jorgensen, Torben, Bork, Peer, Guarner, Francisco, Pedersen, Oluf, Consortium, MetaHit, Sommer, Morten O. A., Ehrlich, S. Dusko, Sicheritz-Ponten, Thomas, Brunak, Soren, Nielsen, H. Bjorn, Almeida, Mathieu, Batto, Jean-Michel, Blottiere, Herve, Cultrone, Antonietta, Delorme, Christine, derwyn, rozenn, Guédon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kennedy, Sean P., Kaci, Ghalia, Layec, Séverine, Leclerc, Marion, Léonard, Pierre, Maguin, Emmanuelle, Pons, Nicolas, Renault, Pierre, Sanchez, Nicolas, Van De Guchte, Maarten, Van Hylckama Vlieg, Johan, Vandemeulebrouck, Gaetana, Winogradsky, Yohanan, Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark [Lyngby] (DTU), A/S, Clinical-Microbiomics, Novo Nordisk Foundation Center for Biosustainability, Department of Systems Biology, DTU Multi-Assay Core, Digestive System Research Unit, Vall d'Hebron University Hospital, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Faculty of Health Sciences, University of Southern Denmark (SDU), Faculty of Medicine, Aalborg University [Denmark] (AAU), Research Centre for Prevention and Health, Capital region, Glostrup University Hospital, University of Copenhagen = Københavns Universitet (KU), European Molecular Biology Laboratory [Hamburg] (EMBL), Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, King‘s College London, Disease Systems Biology [Copenhagen], Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, Clinical Microbiomics, International Human Microbiome Standards [FP7-HEALTH-2010-261376], Metagenopolis [ANR-11-DPBS-0001], Novo Nordisk Foundation, Lundbeck Foundation, European Project: 201052, Vall d'Hebron University Hospital [Barcelona], Génie et Microbiologie des Procédés Alimentaires (GMPA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH), and University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences

Subjects
0301 basic medicine, Microbiology (medical), Feces/microbiology, Systems Analysis, ATP-Binding Cassette Transporters/genetics, Denmark, [SDV]Life Sciences [q-bio], Microbial Interactions/genetics, 030106 microbiology, Immunology, Gastrointestinal Microbiome/genetics, Biology, Applied Microbiology and Biotechnology, Microbiology, 03 medical and health sciences, Feces, Microbial ecology, Journal Article, Genetics, Humans, Butyrates/metabolism, Microbiome, Regulation of gene expression, Ecology, Metabolic Networks and Pathways/genetics, Gene Expression Profiling, Niche segregation, Chemotaxis, Cell Biology, Carbon Dioxide, Gastrointestinal Microbiome, Gene expression profiling, Butyrates, 030104 developmental biology, Metagenomics, Spain, Bifidobacterium bifidum/genetics, Metagenome, Microbial Interactions, Carbon Dioxide/metabolism, ATP-Binding Cassette Transporters, Bifidobacterium bifidum, Adaptation, Metabolic Networks and Pathways
Abstract

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species 2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H 2 and CO 2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.

Published
2016
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13. Prediction of the intestinal resistome by a novel 3D-based method

Author

Ruppé, Etienne, primary, Ghozlane, Amine, additional, Tap, Julien, additional, Pons, Nicolas, additional, Alvarez, Anne-Sophie, additional, Maziers, Nicolas, additional, Cuesta, Trinidad, additional, Hernando-Amado, Sara, additional, Martínez, Jose Luís, additional, Coque, Teresa M., additional, Baquero, Fernando, additional, Lanza, Val F., additional, Maiz, Luis, additional, Goulenok, Tiphaine, additional, Lastours, Victoire de, additional, Amor, Nawal, additional, Fantin, Bruno, additional, Wieder, Ingrid, additional, Andremont, Antoine, additional, Schaik, Willem van, additional, Rogers, Malbert, additional, Zhang, Xinglin, additional, Willems, Rob J.L., additional, De Brevern, Alexandre G., additional, Batto, Jean-Michel, additional, Blottière, Hervé, additional, Léonard, Pierre, additional, Léjard, Véronique, additional, Letur, Aline, additional, Levenez, Florence, additional, Weiszer, Kevin, additional, Haimet, Florence, additional, Doré, Joël, additional, Kennedy, Sean P., additional, and Dusko Ehrlich, S., additional

Published
2017
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14. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

Author

Forslund, Kristoffer, Hildebrand, Falk, Nielsen, Trine, Falony, Gwen, Le Chatelier, Emmanuelle, Sunagawa, Shinichi, Prifti, Edi, Vieira-Silva, Sara, Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Arumugam, Manimozhiyan, Kristiansen, Karsten, Voigt, Anita Yvonne, Vestergaard, Henrik, Hercog, Rajna, Costea, Paul Igor, Kultima, Jens Roat, Li, Junhua, Jorgensen, Torben, Levenez, Florence, Dore, Joel, Consortium, MetaHit, Nielsen, H. Bjorn, Brunak, Soren, Raes, Jeroen, Hansen, Torben, Wang, Jun, Ehrlich, Dusko S, Bork, Peer, Pedersen, Oluf, Almeida, Mathieu, Batto, Jean-Michel, Blottiere, Hervé H, Cultrone, Antonietta, Delorme, Christine, derwyn, rozenn, Guédon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kennedy, Sean P., Kaci, Ghalia, Layec, Séverine, Leclerc, Marion, Léonard, Pierre, Maguin, Emmanuelle, Pons, Nicolas, Renault, Pierre, Sanchez, Nicolas, Van De Guchte, Maarten, Van Hylckama Vlieg, Johan, Vandemeulebrouck, Gaetana, Winogradsky, Yohanan, Structural and Computational Biology Unit, European Molecular Biology Laboratory [Hamburg] (EMBL), VIB Center for the Biology of Disease, Université Catholique de Louvain = Catholic University of Louvain (UCL), Department of Bioscience Engineering, Vrije Universiteit Brussel (VUB), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark [Lyngby] (DTU), Department of Biology [Copenhagen], Faculty of Science [Copenhagen], Molecular Medicine Partnership Unit, Heidelberg University, Department of Applied Tumor Biology, Institute of Pathology, Beijing Genomics Institute [Shenzhen] (BGI), Faculty of Medicine, Aalborg University [Denmark] (AAU), Research Centre for Prevention and Health, Capital Region of Denmark, Department of Public Health [Copenhagen], Disease Systems Biology [Copenhagen], Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, Faculty of Health Sciences, University of Southern Denmark (SDU), Macau University of Science and Technology (MUST), Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong (HKU), Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, King‘s College London, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Department of Bioinformatics, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Génie et Microbiologie des Procédés Alimentaires (GMPA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Département Microbiologie et Chaîne Alimentaire (MICA), Metagenopolis grant ANR-11-DPBS-0001, European Research Council 268985, European Union 600375, Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp), Novo Nordisk Foundation NNF14CC0001, European Molecular Biology Laboratory (EMBL), Novo Nordisk Foundation, Innovation Fund Denmark through the MicrobDiab project, European Project: 201052, Faculty of Sciences and Bioengineering Sciences, Department of Bio-engineering Sciences, Microbiology, Université Catholique de Louvain, Vrije Universiteit [Brussels] (VUB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], University of Heidelberg, Beijing Genomics Institute, Max Delbrück Center for Molecular Medicine, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, and Julius-Maximilians-Universität Würzburg (JMU)

Subjects
Male, Diabetes Mellitus, Type 2/drug therapy, endocrine system diseases, GENOMES, CLOSTRIDIUM, Biology, Microbiology, DISEASE, Article, GLUCOSE, Hypoglycemic Agents/pharmacology, Metformin/pharmacology, RNA, Ribosomal, 16S, Nondestructive testing, Forensic engineering, Hypoglycemic Agents, risk factors, Humans, Gastrointestinal Microbiome/drug effects, Metagenome/drug effects, RNA, Ribosomal, 16S/genetics, Multidisciplinary, IDENTIFICATION, SEQUENCES, business.industry, Biodiversity, CANCER, Metformin, Computational biology and bioinformatics, 3. Good health, Gastrointestinal Microbiome, METAGENOME, Diabetes Mellitus, Type 2, SP-NOV, Female, HEALTH, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

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. ispartof: Nature vol:528 issue:7581 pages:262-6 ispartof: location:England status: published

Published
2015
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15. Quality control of microbiota metagenomics by k-mer analysis

Author

Plaza Onate, Florian, Batto, Jean-Michel, Juste, Catherine, Fadlallah, Jehane, Fougeroux, Cyrielle, Gouas, Doriane, Pons, Nicolas, Kennedy, Sean, Levenez, Florence, Dore, Joel, Dusko Ehrlich, S., Gorochov, Guy, Larsen, Martin, INRA US1367 MetaGenoPolis, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), The study was funded by INSERM, the University Pierre et Marie Curie ËMERGENCE' program, Fondation pour l’Aide a la Recherche sur la Sclerose En Plaques (ARSEP), ARTHRITIS Fondation COURTIN and Agence nationale de la recherché (ANR)., The authors acknowledge the funding agencies and the volunteers providing samples for the study., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Administateur, HAL Sorbonne Université

Subjects
Sample size limits, Quality control, Sampling bias, Metagenomics, Next generation sequencing, MESH: Bacteria/genetics, MESH: Quality Control, Médecine humaine et pathologie, MESH: Metagenomics/standards, MESH: Genome, Bacterial, Sensitivity and Specificity, Feces, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Cluster Analysis, Humans, MESH: Gastrointestinal Tract/microbiology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, Bacteria, Methodology Article, Microbiota, MESH: Feces/microbiology, MESH: Metagenome, MESH: Microbiota, MESH: Cluster Analysis, MESH: Sensitivity and Specificity, MESH: Metagenomics/methods, Gastrointestinal Tract, MESH: Bacteria/classification, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Metagenome, Human health and pathology, Genome, Bacterial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biotechnology
Abstract

Background The biological and clinical consequences of the tight interactions between host and microbiota are rapidly being unraveled by next generation sequencing technologies and sophisticated bioinformatics, also referred to as microbiota metagenomics. The recent success of metagenomics has created a demand to rapidly apply the technology to large case–control cohort studies and to studies of microbiota from various habitats, including habitats relatively poor in microbes. It is therefore of foremost importance to enable a robust and rapid quality assessment of metagenomic data from samples that challenge present technological limits (sample numbers and size). Here we demonstrate that the distribution of overlapping k-mers of metagenome sequence data predicts sequence quality as defined by gene distribution and efficiency of sequence mapping to a reference gene catalogue. Results We used serial dilutions of gut microbiota metagenomic datasets to generate well-defined high to low quality metagenomes. We also analyzed a collection of 52 microbiota-derived metagenomes. We demonstrate that k-mer distributions of metagenomic sequence data identify sequence contaminations, such as sequences derived from “empty” ligation products. Of note, k-mer distributions were also able to predict the frequency of sequences mapping to a reference gene catalogue not only for the well-defined serial dilution datasets, but also for 52 human gut microbiota derived metagenomic datasets. Conclusions We propose that k-mer analysis of raw metagenome sequence reads should be implemented as a first quality assessment prior to more extensive bioinformatics analysis, such as sequence filtering and gene mapping. With the rising demand for metagenomic analysis of microbiota it is crucial to provide tools for rapid and efficient decision making. This will eventually lead to a faster turn-around time, improved analytical quality including sample quality metrics and a significant cost reduction. Finally, improved quality assessment will have a major impact on the robustness of biological and clinical conclusions drawn from metagenomic studies. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1406-7) contains supplementary material, which is available to authorized users.

Published
2015
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16. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome

Author

Shoaie, Saeed, Ghaffari, Pouyan, Kovatcheva-Datchary, Petia, Mardinoglu, Adil, Sen, Partho, Pujos-Guillot, Estelle, De Wouters, Tomas, Juste, Catherine, Rizkalla, Salwa, Chilloux, Julien, Hoyles, Lesley, Nicholson, Jeremy K., Consortium, MICRO-Obes, Doré, Joël, Dumas, Marc E., Clément, Karine, Bäckhed, Fredrik, Nielsen, Jens, Kennedy, Sean P., Prifti, Edi, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Levenez, Florence, Galleron, Nathalie, Batto, Jean-Michel, Ehrlich, Stanislav, Blottiere, Herve, Lepage, Patricia, Maguin, Emmanuelle, Van De Guchte, Maarten, Department of Biology and Biological Engineering, Chalmers University of Technology [Göteborg], University of Gothenburg (GU), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Plateforme d'Exploration du Métabolisme, Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MetaGenoPolis, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imperial College London, University of Copenhagen = Københavns Universitet (KU), Département Microbiologie et Chaîne Alimentaire (MICA), Knut and Alice Wallenberg Foundation, Bill & Melinda Gates Foundation, Torsten Soderbergs Stiftelse, European Commission HEALTH-F4-2012-305312, Fondation Coeur et Arteres, French National Agency of Research (ANR MicroObes and 'Investissements d'avenir') ANR-10-IAHU-05, ProdInra, Migration, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Copenhagen = Københavns Universitet (UCPH), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Commission of the European Communities, and Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, HOST, Interactive optimization, Physiology, Genome scale, Microbial metabolism, Computational biology, Gut flora, Bioinformatics, Models, Biological, MICROFLORA, Endocrinology & Metabolism, RECONSTRUCTIONS, 03 medical and health sciences, 0302 clinical medicine, Human gut, MICRO-Obes Consortium, 1101 Medical Biochemistry And Metabolomics, Humans, Metabolic modeling, AMINO-ACIDS, Microbiome, Intestinal Mucosa, Molecular Biology, Feces, 030304 developmental biology, 0303 health sciences, Science & Technology, biology, Microbiota, 0601 Biochemistry And Cell Biology, Cell Biology, biology.organism_classification, GENE, Intestines, PROTEIN-COUPLED RECEPTOR, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, CHAIN FATTY-ACIDS, HUMAN LARGE-INTESTINE, BACTERIA, Female, ADIPOSITY, Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

International audience; The 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.

Published
2015
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17. Richness of human gut microbiome correlates with metabolic markers

Author

Lechatelier, Emmanuelle, Nielsen, Trine, Qin, Junjie, Prifti, Edi, Hildebrand, Falk, Falony, Gwen, Almeida, Mathieu, Arumugam, Manimozhiyan, Batto, Jean-Michel, Kennedy, S., Léonard, Pe, Li, J., Burgdorf, Kristoffer Solvsten, Grarup, Niels, Raes, Jeroen, Jorgensen, Torben, and Department of Bio-engineering Sciences

Subjects
human, gut
Abstract

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.

Published
2013

18. Characterization of the gut microbiota by quantitative metagenomics: a promising tool for risk stratification in NAFLD patients

Author

Ratziu, V., Pichaud, M., Fedchuk, L., Levenez, Florence, Quinquis, Benoit, Galleron, Nathalie, Batto, Jean-Michel, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Kennedy, Sean, Doré, Joël, Ehrlich, Stanislav, Rimbaud, P., CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Enterome Bioscience, Association Recherche Maladies Hépatiques Virales, Partenaires INRAE, MetaGenoPolis, and Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], nafld, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

19. Prevalence of streptococci in the intestinal flora

Author

Almeida, Mathieu, Le Chatelier, Emmanuelle, Pons, Nicolas, Achouri, Emna, Layec, Séverine, Moumen, Bouziane, Batto, Jean-Michel, Boumezbeur, Fouad, Kennedy, Sean, Delorme, Christine, Guedon, Eric, Ehrlich, Stanislav, Renault, Pierre, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biomics, Centre de Recherche et Innovation Technologique (CITECH), Institut Pasteur [Paris]-Institut Pasteur [Paris], Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
streptococcusi, flore intestinale, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

absent

Published
2012

20. Metagenomics of the intestinal microbiota: potential applications

Author

Dusko, Ehrlich S., Antolin, Maria, Artiquenave, François, Arumugam, Manimozhiyan, Batto, Jean-Michel, Bertalan, Marcelo, Blottiere, Hervé M., Bork, Peer, Borruel, Natalia, Brechot, Christian, Brunak, Soren, Bruls, Thomas, Burgdorf, Kristoffer Solvsten, Cao, Jianjun, Casellas, Francesc, Chervaux, Christian, Colombel, Jean Frédérique, Cultrone, Antonella, Doré, Joel, Delorme, Christine, Denariaz, Gérard, Dervyn, Rozenn, Forte, Miguel, Friss, Carsten, Guarner, Francisco, Van De Guchte, Maarten, Guedon, Eric, Haimet, Florence, Hansen, Torben, Jamet, Alexandre, Jian, Min, Juste, Catherine, Kaci, Ghalia, Kleerebezem, Michiel, Knol, Jan, Kristiansen, Karsten, Layec, Severine, Le Roux, Karine, Marion, Leclerc, Le Paslier, Denis, Levenez, Florence, Li, Dong, Li, Jun, Li, Shaochuan, Li, Songgang, Li, Shengting, Yingrui, Li, Liang, Huiqing, Mende, Daniel R., Maguin, Emmanuelle, Manichanh, Chaysavanh, Minardi, Raquel Melo, Mrini, Christine, Nielsen, H. Bjorn, Nielsen, Trine, Oozeer, Raish, Parkhill, Julian, Pons, Nicolas, Pedersen, Oluf, Pelletier, Eric, Qin, Junjie, Raes, Jeroen, Renault, Pierre, Rescigno, Maria, Li, Ruiqiang, Sanchez, Nicolas, Sicheritz-Ponten, Thomas, Sebastian, Tims, Torrejon, Antonio, Turner, Keith, Encarna, Varela, Wang, Bo, Wang, Jian, Wang, Jun, Weissenbach, Jean, Winogradsky, Yohanan, Xie, Ying, Xu, Junming, Yamada, Takuji, Yang, Huanming, Yu, Chang, Zheng, Huisong, Zhang, Xiuqing, Zhu, Hongmei, Zhou, Yan, Zoetendal, Erwin G, De Vos, Willem, and Department of Bio-engineering Sciences

Subjects
xxx
Abstract

A major challenge in the human metagenomics field is to identify associations of the bacterial genes and human phenotypes and act to modulate microbial populations in order to improve human health and wellbeing. MetaHIT project addresses this ambitious challenge by developing and integrating a number of necessary approaches within the context of the gut microbiome. Among the first results is the establishment of a broad catalog of the human gut microbial genes, which was achieved by an original application of the new generation sequencing technology. The catalog contains 3.3 million non-redundant genes, 150-fold more than the human genome equivalent and includes a large majority of the gut metagenomic sequences determined across three continents, Europe, America and Asia. Its content corresponds to some 1000 bacterial species, which likely represent a large fraction of species associated with humankind intestinal tract. The catalog enables development of the gene profiling approaches aiming to detect associations of bacterial genes and phenotypes. These should lead to the speedy development of diagnostic and prognostic tools and open avenues to reasoned approaches to the modulation of the individual's microbiota in order to optimize health and well-being.

Published
2010

21. Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products

Author

Almeida, Mathieu, Almeida, Mathieu, Hébert, Agnès, Abraham, Anne-Laure, Rasmussen, Simon, Monnet, Christophe, Pons, Nicolas, Delbès, Céline, Loux, Valentin, Batto, Jean-Michel, Leonard, Pierre, Kennedy, Sean, Ehrlich, Stanislas Dusko, Pop, Mihai, Montel, Marie-Christine, Irlinger, Françoise, Renault, Pierre, Almeida, Mathieu, Almeida, Mathieu, Hébert, Agnès, Abraham, Anne-Laure, Rasmussen, Simon, Monnet, Christophe, Pons, Nicolas, Delbès, Céline, Loux, Valentin, Batto, Jean-Michel, Leonard, Pierre, Kennedy, Sean, Ehrlich, Stanislas Dusko, Pop, Mihai, Montel, Marie-Christine, Irlinger, Françoise, and Renault, Pierre

Abstract

Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned. We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study. Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods.

Published
2014

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

Author

Nielsen, H Bjørn, Almeida, Mathieu, Juncker, Agnieszka, Rasmussen, Simon, Li, Junhua, Sunagawa, Shinichi, Plichta, Damian Rafal, Gautier, Laurent, Pedersen, Anders G., Le Chatelier, Emmanuelle, Pelletier, Eric, Bonde, Ida, Nielsen, Trine, Manichanh, Chaysavanh, Arumugam, Manimozhiyan, Batto, Jean-Michel, dos Santos, Marcelo Bertalan Quintanilha, Blom, Nikolaj, Borruel, Natalia, Burgdorf, Kristoffer Sølvsten, Boumezbeur, Fouad, Casellas, Francesc, Doré, Joël, Dworzynski, Piotr, Guarner, Francisco, Hansen, Torben, Hildebrand, Falk, Kaas, Rolf Sommer, Kennedy, Sean, Kristiansen, Karsten, Kultima, Jens Roat, Léonard, Pierre, Levenez, Florence, Lund, Ole, Moumen, Bouziane, Le Paslier, Denis, Pons, Nicolas, Pedersen, Oluf Borbye, Prifti, Edi, Qin, Junjie, Raes, Jeroen, Sørensen, Søren Johannes, Tap, Julien, Tims, Sebastian, Ussery, David, Yamada, Takuji, Renault, Pierre, Sicheritz-Pontén, Thomas, Bork, Peer, Wang, Jun, Nielsen, H Bjørn, Almeida, Mathieu, Juncker, Agnieszka, Rasmussen, Simon, Li, Junhua, Sunagawa, Shinichi, Plichta, Damian Rafal, Gautier, Laurent, Pedersen, Anders G., Le Chatelier, Emmanuelle, Pelletier, Eric, Bonde, Ida, Nielsen, Trine, Manichanh, Chaysavanh, Arumugam, Manimozhiyan, Batto, Jean-Michel, dos Santos, Marcelo Bertalan Quintanilha, Blom, Nikolaj, Borruel, Natalia, Burgdorf, Kristoffer Sølvsten, Boumezbeur, Fouad, Casellas, Francesc, Doré, Joël, Dworzynski, Piotr, Guarner, Francisco, Hansen, Torben, Hildebrand, Falk, Kaas, Rolf Sommer, Kennedy, Sean, Kristiansen, Karsten, Kultima, Jens Roat, Léonard, Pierre, Levenez, Florence, Lund, Ole, Moumen, Bouziane, Le Paslier, Denis, Pons, Nicolas, Pedersen, Oluf Borbye, Prifti, Edi, Qin, Junjie, Raes, Jeroen, Sørensen, Søren Johannes, Tap, Julien, Tims, Sebastian, Ussery, David, Yamada, Takuji, Renault, Pierre, Sicheritz-Pontén, Thomas, Bork, Peer, and Wang, Jun

Abstract

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.

Published
2014

23. Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products

Author

Almeida, Mathieu, primary, Hébert, Agnès, additional, Abraham, Anne-Laure, additional, Rasmussen, Simon, additional, Monnet, Christophe, additional, Pons, Nicolas, additional, Delbès, Céline, additional, Loux, Valentin, additional, Batto, Jean-Michel, additional, Leonard, Pierre, additional, Kennedy, Sean, additional, Ehrlich, Stanislas Dusko, additional, Pop, Mihai, additional, Montel, Marie-Christine, additional, Irlinger, Françoise, additional, and Renault, Pierre, additional

Published
2014
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24. Lactobacillus delbrueckii ssp. lactis and ssp. bulgaricus: a chronicle of evolution in action

Author

El Kafsi, Hela, primary, Binesse, Johan, additional, Loux, Valentin, additional, Buratti, Julien, additional, Boudebbouze, Samira, additional, Dervyn, Rozenn, additional, Kennedy, Sean, additional, Galleron, Nathalie, additional, Quinquis, Benoît, additional, Batto, Jean-Michel, additional, Moumen, Bouziane, additional, Maguin, Emmanuelle, additional, and van de Guchte, Maarten, additional

Published
2014
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25. Enterotypes of the human gut microbiome:[Plus]Corrigendum [Plus]Addendum

Author

Arumugam, Manimozhiyan, Raes, Jeroen, Pelletier, Eric, Le Paslier, Denis, Yamada, Takuji, Mende, Daniel R, Fernandes, Gabriel R, Tap, Julien, Bruls, Thomas, Batto, Jean-Michel, dos Santos, Marcelo Bertalan Quintanilha, Borruel, Natalia, Casellas, Francesc, Fernandez, Leyden, Gautier, Laurent, Hansen, Torben, Hattori, Masahira, Hayashi, Tetsuya, Kleerebezem, Michiel, Kurokawa, Ken, Leclerc, Marion, Levenez, Florence, Manichanh, Chaysavanh, Nielsen, H Bjørn, Nielsen, Trine, Pons, Nicolas, Poulain, Julie, Qin, Junjie, Sicheritz-Ponten, Thomas, Tims, Sebastian, Torrents, David, Ugarte, Edgardo, Zoetendal, Erwin G, Wang, Jun, Guarner, Francisco, Pedersen, Oluf, de Vos, Willem M, Brunak, Søren, Doré, Joel, Antolín, María, Artiguenave, François, Blottiere, Hervé M, Almeida, Mathieu, Brechot, Christian, Cara, Carlos, Chervaux, Christian, Cultrone, Antonella, Delorme, Christine, Denariaz, Gérard, Kristiansen, Karsten, Arumugam, Manimozhiyan, Raes, Jeroen, Pelletier, Eric, Le Paslier, Denis, Yamada, Takuji, Mende, Daniel R, Fernandes, Gabriel R, Tap, Julien, Bruls, Thomas, Batto, Jean-Michel, dos Santos, Marcelo Bertalan Quintanilha, Borruel, Natalia, Casellas, Francesc, Fernandez, Leyden, Gautier, Laurent, Hansen, Torben, Hattori, Masahira, Hayashi, Tetsuya, Kleerebezem, Michiel, Kurokawa, Ken, Leclerc, Marion, Levenez, Florence, Manichanh, Chaysavanh, Nielsen, H Bjørn, Nielsen, Trine, Pons, Nicolas, Poulain, Julie, Qin, Junjie, Sicheritz-Ponten, Thomas, Tims, Sebastian, Torrents, David, Ugarte, Edgardo, Zoetendal, Erwin G, Wang, Jun, Guarner, Francisco, Pedersen, Oluf, de Vos, Willem M, Brunak, Søren, Doré, Joel, Antolín, María, Artiguenave, François, Blottiere, Hervé M, Almeida, Mathieu, Brechot, Christian, Cara, Carlos, Chervaux, Christian, Cultrone, Antonella, Delorme, Christine, Denariaz, Gérard, and Kristiansen, Karsten

Abstract

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

Published
2011

26. Addendum: Enterotypes of the human gut microbiome

Author

Arumugam, Manimozhiyan, primary, Raes, Jeroen, additional, Pelletier, Eric, additional, Le Paslier, Denis, additional, Yamada, Takuji, additional, Mende, Daniel R., additional, Fernandes, Gabriel R., additional, Tap, Julien, additional, Bruls, Thomas, additional, Batto, Jean-Michel, additional, Bertalan, Marcelo, additional, Borruel, Natalia, additional, Casellas, Francesc, additional, Fernandez, Leyden, additional, Gautier, Laurent, additional, Hansen, Torben, additional, Hattori, Masahira, additional, Hayashi, Tetsuya, additional, Kleerebezem, Michiel, additional, Kurokawa, Ken, additional, Leclerc, Marion, additional, Levenez, Florence, additional, Manichanh, Chaysavanh, additional, Nielsen, H. Bjørn, additional, Nielsen, Trine, additional, Pons, Nicolas, additional, Poulain, Julie, additional, Qin, Junjie, additional, Sicheritz-Ponten, Thomas, additional, Tims, Sebastian, additional, Torrents, David, additional, Ugarte, Edgardo, additional, Zoetendal, Erwin G., additional, Wang, Jun, additional, Guarner, Francisco, additional, Pedersen, Oluf, additional, de Vos, Willem M., additional, Brunak, Søren, additional, Doré, Joel, additional, Consortium, MetaHIT, additional, Weissenbach, Jean, additional, Ehrlich, S. Dusko, additional, and Bork, Peer, additional

Published
2014
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27. Erratum: Corrigendum: Dietary intervention impact on gut microbial gene richness

Author

Cotillard, Aurélie, primary, Kennedy, Sean P., additional, Kong, Ling Chun, additional, Prifti, Edi, additional, Pons, Nicolas, additional, Le Chatelier, Emmanuelle, additional, Almeida, Mathieu, additional, Quinquis, Benoit, additional, Levenez, Florence, additional, Galleron, Nathalie, additional, Gougis, Sophie, additional, Rizkalla, Salwa, additional, Batto, Jean-Michel, additional, Renault, Pierre, additional, consortium, ANR MicroObes, additional, Doré, Joel, additional, Zucker, Jean-Daniel, additional, Clément, Karine, additional, and Ehrlich, Stanislav Dusko, additional

Published
2013
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28. Genomic Characterization of the Taylorella Genus

Author

Hébert, Laurent, primary, Moumen, Bouziane, additional, Pons, Nicolas, additional, Duquesne, Fabien, additional, Breuil, Marie-France, additional, Goux, Didier, additional, Batto, Jean-Michel, additional, Laugier, Claire, additional, Renault, Pierre, additional, and Petry, Sandrine, additional

Published
2012
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31. Development of Software Facilities to Characterize Regulatory Binding Motifs and Application to Streptococcaceae.

Author

Pons, Nicolas, Batto, Jean-Michel, Ehrlich, Stanislav Dusko, and Renault, Pierre

Subjects
*STREPTOCOCCACEAE, *GENE expression, *NUCLEOTIDE sequence, *COMPUTER software development, *GENETIC regulation
Abstract

Gene expression regulation often involves the recognition of particular DNA or RNA sequences, called motifs. Detection and characterization of such motifs together with biological expertise allow to build gene expression regulatory maps that facilitate the comprehension of complex cellular processes. In this frame, we developed a software integrating relevant information for the detection and characterization of conserved motifs in genomic sequences. A relational database was built up to host data related to genomic information and transcriptional experiments. A user-friendly interface was designed to allow a convenient representation of these data and to run the detection motif program. A set of complementary utilities was also developed to improve the determination of motif consensus sequences and the detection of additional potential regulator targets in the genome. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2007
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32. Human gut microbes impact host serum metabolome and insulin sensitivity

Author

Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Nielsen, Henrik Bjørn, Hyotylainen, Tuulia, Nielsen, Trine, Jensen, Benjamin A H, Forslund, Kristoffer, Hildebrand, Falk, Prifti, Edi, Falony, Gwen, Le Chatelier, Emmanuelle, Levenez, Florence, Dore, Joel, Mattila, Ismo, Plichta, Damian R, Pöhö, Päivi, Hellgren, Lars I, Arumugam, Manimozhiyan, Sunagawa, Shinichi, Vieira-Silva, Sara, Jørgensen, Torben, Holm, Jacob Bak, Trošt, Kajetan, Kristiansen, Karsten, Brix, Susanne, Raes, Jeroen, Wang, Jun, Hansen, Torben, Bork, Peer, Brunak, Søren, Oresic, Matej, Ehrlich, S. Dusko, Pedersen, Oluf, MetaHIT Consortium, ., Almeida, Mathieu, Batto, Jean-Michel, Blottiere, Hervé, Cultrone, Antonietta, Delorme, Christine, Dervyn, Rozenn, Guedon, Eric, Haimet, Florence, Jamet, Alexandre, Juste, Catherine, Kennedy, Sean, Kaci, Ghalia, Kleerebezem, Michiel, Layec, Séverine, Leclerc, Marion, Léonard, Pierre, Maguin, Emmanuelle, Manichanh, Chaysavanh, Pons, Nicolas, Renault, Pierre, Sanchez, Nicolas, Van De Guchte, Maarten, Van Hylckama Vlieg, Johan, Vandemeulebrouck, Gaetana, Winogradsky, Yohanan, Center for Biological Sequence Analysis - Department of Systems Biology, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Denmark, Turku Centre for Biotechnology, University of Turku-Åbo Academy University, Åbo Akademi University [Turku], Örebro University, VTT Technical Research Centre of Finland (VTT), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Laboratory of Genomics and Molecular Biomedicine - Department of Biology, University of Copenhagen = Københavns Universitet (UCPH), European Molecular Biology Laboratory, Department of Bioscience Engineering, University of Antwerp (UA), Center for the Biology of Disease, VIB, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centter for the Biology of Disease, Department of Microbiology and Immunology, Rega Institute for Medical Research, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Steno Diabetes Center, Faculty of Pharmacy, University of Valencia, Institute of Microbiology, Université de Lausanne = University of Lausanne (UNIL), Centre for the Biology of Disease, Research Centre for Prevention and Health - Centre for Health, Glostrup Hospital, Beijing Genomics Institute [Shenzhen] (BGI), Vrije Universiteit Brussel [Bruxelles] (VUB), Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Macau University of Science and Technology (MUST), Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Faculty of Health Sciences, Aarhus University [Aarhus], Molecular Medicine Partnership Unit, Heidelberg University, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Department of Bioinformatics, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Disease Systems Biology [Copenhagen], Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, Centre for Biotechnology, Silesian University of Technology, Université Paris-Saclay, Centre for Host–Microbiome Interactions - Dental Institute Central Office, King‘s College London, Guys Hospital, Génie et Microbiologie des Procédés Alimentaires (GMPA), Département Microbiologie et Chaîne Alimentaire (MICA), Danone Research, Groupe Danone, International Human Microbiome Standards [FP7-HEALTH-2010-261376], Metagenopolis [ANR-11-DPBS-0001], Novo Nordisk Foundation, Lundbeck Foundation, European Project: 222720,EC | FP7 | SP1 | KBBE ,FP7-KBBE-2007-2A,TORNADO(2009), Technical University of Denmark [Lyngby] (DTU), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Copenhagen = Københavns Universitet (KU), Jouy-en-Josas, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Université de Lausanne (UNIL), BGI Shenzhen, Vrije University, University of Heidelberg, Max Delbrück Center for Molecular Medicine, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, US 1367 MGP MetaGénoPolis, Laboratory of Microbiology, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Digestive System Research Unit, Vall d'Hebron University Hospital [Barcelona], European Project: 201052, Faculty of Sciences and Bioengineering Sciences, Microbial Interactions, Department of Bio-engineering Sciences, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Prevotella, Gastrointestinal Microbiome/physiology, Bacteroides/physiology, Type 2 diabetes, Fasting/blood, SERUM, Mice, 0302 clinical medicine, insulin resistance, Bacteroides, Netherlands, Multidisciplinary, biology, Research Support, Non-U.S. Gov't, Gastrointestinal Microbiome, Prevotella/physiology, Fasting, 3. Good health, Cardiovascular diseases, Cardiovascular Diseases/metabolism, Metabolome, Amino Acids, Branched-Chain/biosynthesis, medicine.medical_specialty, Glyco-Forum Section, Serum/metabolism, mice, 030209 endocrinology & metabolism, metagenome, 03 medical and health sciences, Insulin resistance, Internal medicine, Glucose Intolerance, medicine, Animals, Humans, Microbiome, Glucose Intolerance/blood, ta1182, biology.organism_classification, medicine.disease, Obesity, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Metagenome, Insulin Resistance, Amino Acids, Branched-Chain
Abstract

MetaHIT Consortium: Almeida M, Antolin M, Artiguenave F, Batto JM, Bertalan M, Blottiere H, Boruel N, Brechot C, Bruls T, Burgdorf K, Casellas F, Cultrone A, de Vos WM, Delorme C, Denariaraz G., Derrien M, Dervyn R, Feng Q, Grarup N, Guarner F, Guedon E, Haimet F, Jamet A, Juncker A, Juste C, Kennedy S, Khaci G, Kleerebezem M, Knoll J, Layec S, Leclerc M, Leonard P, LePaslier D, m'Rini C, Maguin E, Manichanh C, Mende D, Merieux A, Oozer R, Parkhill J, Pelletier E, POns N, QinJ, rasmussen S, Renault P, Rescigno M, Sanchez N, Sicheritz-Ponten T, Tap J, Tims S, Torrejon A, Turner K, van de Guchet M, van hylckama Vlieg JE, Vandemeulebrouck G, Varela E, Veiga P, Weissenbach J, Winogradski Y, Yamada T, Zoetendal EG; 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.

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33. Elevated serum ceramides are linked with obesity-associated gut dysbiosis and impaired glucose metabolism.

Author

Kayser, Brandon D., Prifti, Edi, Lhomme, Marie, Belda, Eugeni, Dao, Maria-Carlota, Aron-Wisnewsky, Judith, MICRO-Obes Consortium, Cotillard, Aurélie, Kennedy, Sean P., Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Galleron, Nathalie, Batto, Jean-Michel, Renault, Pierre, Ehrlich, Stanislav Dusko, Blottière, Hervé, Leclerc, Marion, and de Wouters, Tomas

Subjects
CERAMIDES, GLUCOSE metabolism, LIPID metabolism disorders, GUT microbiome, SHOTGUN sequencing, LIPID metabolism
Abstract

Introduction: Low gut microbiome richness is associated with dyslipidemia and insulin resistance, and ceramides and other sphingolipids are implicated in the development of diabetes. Objectives: Determine whether circulating sphingolipids, particularly ceramides, are associated with alterations in the gut microbiome among obese patients with increased diabetes risk. Methods: This was a cross-sectional and longitudinal retrospective analysis of a dietary/weight loss intervention. Fasted serum was collected from 49 participants (41 women) and analyzed by HPLC–MS/MS to quantify 45 sphingolipids. Shotgun metagenomic sequencing of stool was performed to profile the gut microbiome. Results: Confirming the link to deteriorated glucose homeostasis, serum ceramides were positively correlated with fasting glucose, but inversely correlated with fasting and OGTT-derived measures of insulin sensitivity and β-cell function. Significant associations with gut dysbiosis were demonstrated, with SM and ceramides being inversely correlated with gene richness. Ceramides with fatty acid chain lengths of 20–24 carbons were the most associated with low richness. Diet-induced weight loss, which improved gene richness, decreased most sphingolipids. Thirty-one MGS, mostly corresponding to unidentified bacteria species, were inversely correlated with ceramides, including a number of Bifidobacterium and Methanobrevibacter smithii. Higher ceramide levels were also associated with increased metagenomic modules for lipopolysaccharide synthesis and flagellan synthesis, two pathogen-associated molecular patterns, and decreased enrichment of genes involved in methanogenesis and bile acid metabolism. Conclusion: This study identifies an association between gut microbiota richness, ceramides, and diabetes risk in overweight/obese humans, and suggests that the gut microbiota may contribute to dysregulation of lipid metabolism in metabolic disorders. [ABSTRACT FROM AUTHOR]

Published
2019
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34. Corrigendum: Dietary intervention impact on gut microbial gene richness.

Author

Cotillard, Aurélie, Kennedy, Sean P., Kong, Ling Chun, Prifti, Edi, Pons, Nicolas, Le Chatelier, Emmanuelle, Almeida, Mathieu, Quinquis, Benoit, Levenez, Florence, Galleron, Nathalie, Gougis, Sophie, Rizkalla, Salwa, Batto, Jean-Michel, Renault, Pierre, consortium, ANR MicroObes, Doré, Joel, Zucker, Jean-Daniel, Clément, Karine, and Ehrlich, Stanislav Dusko

Subjects
NUTRITION counseling, MICROBIAL genes
Abstract

A correction to the article "Dietary intervention impact on gut microbial gene richness" that was published in a 2013 issue is presented.

Published
2013
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