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E06 The commensal intestinal microbiota in health and immune diseases
Extended abstracts of the lectures development of diabetes and potentially other autoimmune diseases. Reference(s) [1] Jones EY, Fugger L, Strominger JL, Siebold C. Nat Rev Immunol 2007; 6: 271 82. [2] Nepom GT, Erlich H. Annu Rev Immunol 1991; 9: 493 525. [3] Singh SM, Murphy B, O’Reilly R. Clin Genet. 2002; 62: 97 103. [4] Kodama K, Butte AJ, Creusot RJ, Su L, Sheng D, Hartnett M, Iwai H, Soares LR, Fathman CG. Clin Immunol 2008; 129: 195 201. [5] Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier AR, Turley SJ, Fathman CG, Creusot RJ. Nat Immunol. 2009; 10: 1026 33. Session 3
The gut flora: homeostasis or inflammation
E06 The commensal intestinal microbiota in health and immune diseases J. Dor´ e. Micalis Institute, Institut National del la Recherche Agronomique (INRA), Jouy-en-Josas, Cedex France The human intestinal tract harbours a complex microbial ecosystem which plays a key role in nutrition and health. The key interactions between food constituents, microbes and the host organism derive from a long co-evolution, resulting in a mutualistic association. The rate of discovery of new bacteria of the microbiota remained low as long as culturing was the only method available. Culture-independent molecular tools have resulted in a dramatic increase in the number of gut microbes identified, allowing a complete reassessment of the microbial diversity of the human gut. Although the human faecal microbiota is diverse in its composition, and appeared essentially subject-specific, its functionality is expected to be homogeneous between individuals. However it is not yet clear at which level, metagenome, metaproteome or metabolome, this functional homogeneity can be identified. These different levels of integration have recently become accessible for global exploration of the microbiota. At present, each dominant fecal microbiota is viewed as composed of an average 1000 species, 80% of which will be specific of their host and a limited fraction (approximately 2% of all species) will be conserved among healthy individuals, being altogether more prevalent and also more represented in relative numbers. They constitute a phylogenetic core. At the metaproteomic level, this translates into a high proportion of conserved proteins between microbiota (50 60%). The dominant mucosa associated microbiota appears different from the fecal microbiota and at the same time highly conserved for the different segments of the colon and the terminal ileum. The knowledge gathered from these high throughput molecular assessments allows to define the normal microbiota based on both static and dynamic parameters, related to composition and functions. The qualification of Eubiosis, c.a. the homeostatic context of healthy individuals’ microbiota, allows in turn to explore distortions thereof, hence defining Dysbiosis. This rather novel situation opens perspectives for both mechanistic exploration into the role of Dysbiosis in diseases as well as strategies for reverting Dysbiosis to the homeostatic state of Eubiosis. The current status of investigations into the human faecal metagenome will deliver an extensive gene repertoire representative of functional potentials of the human intestinal microbiota. A reference set of micro-organisms is also currently analysed as part of a concerted effort to sequence the
5 human metagenome, the ensemble of the genomes of humanassociated micro-organisms. Beyond sequence-based human intestinal microbiome explorations, metagenomic libraries will facilitate functional studies. For example, functional screening of the metagenomic libraries allows for the identification of unexplored genomic resources some of which are likely to be highly relevant to our understanding of host-microbe interactions. The International Human Microbiome Consortium aims to give an unprecedented view of the gut microbiota and validate microbial signatures of prognostic and diagnostic value. These approaches promise to identify the most redundant genomic traits of the human intestinal microbiota, thereby identifying the functional balance of this organ. Ultimately it will support the concept of a functional core within the intestinal microbiome. Reference(s) [1] Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh S, Nielsen T, Pons N, Levenez F, Yamada T, Mende D, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto J-M, Hansen T, Le Paslier D, Linneberg A, Bjørn Nielsen H, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Zhang X, Li S, Yang H, Wang J, Brunak S, Dor´ e J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. 2010. A human gut microbial gene catalog established by deep metagenomic sequencing. Nature In Press. [2] Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet J-P, Ugarte E, Mu˜ noz-Tamayo R, Le Paslier D, Nalin R, Dore J, Leclerc M. 2009. Towards the human intestinal microbiota. phylogenetic core. Environmental Microbiology. [3] Sokol H, Pigneur B, Watterlot L, Lakhdari O, BermudezHumaran LG, Gratadoux J-J, Blugeon S, Bridonneau C, Furet J-P, Corthier G, Grangette C, Vasquez N, Pochart Ph, Trugnan G, Thomas G, Blotti` ere HM, Dor´ e J, Marteau P, Seksik P, Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn’s disease patients. Proceedings of the National Academy of Sciences of the United States of America. 2008. E07 Gut microbiota and metabolism at the cross-road between homeostasis and chronic inflammation D. Haller. Chair for Biofunctionality, ZIEL Research Center for Nutrition and Food Science, CDD Center for Diet and Disease, Technische Universit¨ at M¨ unchen, Freising, Germany Lifestyle changes in the industrialized world are associated with a sharp increase in the incidence of chronically degenerative pathologic processes. The hallmark for the development of these chronically degenerative and “lifestyle-dependent” diseases of the modern world implies a complex interaction of genetic predispositions and environmental triggers. Nutritionrelated factors and the high caloric intake (over nutrition) together with components of the gut-associated microbial ecosystem (gut microbiota) emerge as prime environmental triggers for the development and modification of lifestylerelated chronic diseases such as chronic inflammatory disorders of the gastro-intestinal tract as well as metabolic pathologies such as obesity-associated insulin resistance and type 2 diabetes. Epidemiological analysis identified high fat diets to be associated with the progression of obesity-associated comorbidities and/or pathologies [1]. These correlations either
The gut flora: homeostasis or inflammation
E06 The commensal intestinal microbiota in health and immune diseases J. Dor´ e. Micalis Institute, Institut National del la Recherche Agronomique (INRA), Jouy-en-Josas, Cedex France The human intestinal tract harbours a complex microbial ecosystem which plays a key role in nutrition and health. The key interactions between food constituents, microbes and the host organism derive from a long co-evolution, resulting in a mutualistic association. The rate of discovery of new bacteria of the microbiota remained low as long as culturing was the only method available. Culture-independent molecular tools have resulted in a dramatic increase in the number of gut microbes identified, allowing a complete reassessment of the microbial diversity of the human gut. Although the human faecal microbiota is diverse in its composition, and appeared essentially subject-specific, its functionality is expected to be homogeneous between individuals. However it is not yet clear at which level, metagenome, metaproteome or metabolome, this functional homogeneity can be identified. These different levels of integration have recently become accessible for global exploration of the microbiota. At present, each dominant fecal microbiota is viewed as composed of an average 1000 species, 80% of which will be specific of their host and a limited fraction (approximately 2% of all species) will be conserved among healthy individuals, being altogether more prevalent and also more represented in relative numbers. They constitute a phylogenetic core. At the metaproteomic level, this translates into a high proportion of conserved proteins between microbiota (50 60%). The dominant mucosa associated microbiota appears different from the fecal microbiota and at the same time highly conserved for the different segments of the colon and the terminal ileum. The knowledge gathered from these high throughput molecular assessments allows to define the normal microbiota based on both static and dynamic parameters, related to composition and functions. The qualification of Eubiosis, c.a. the homeostatic context of healthy individuals’ microbiota, allows in turn to explore distortions thereof, hence defining Dysbiosis. This rather novel situation opens perspectives for both mechanistic exploration into the role of Dysbiosis in diseases as well as strategies for reverting Dysbiosis to the homeostatic state of Eubiosis. The current status of investigations into the human faecal metagenome will deliver an extensive gene repertoire representative of functional potentials of the human intestinal microbiota. A reference set of micro-organisms is also currently analysed as part of a concerted effort to sequence the
5 human metagenome, the ensemble of the genomes of humanassociated micro-organisms. Beyond sequence-based human intestinal microbiome explorations, metagenomic libraries will facilitate functional studies. For example, functional screening of the metagenomic libraries allows for the identification of unexplored genomic resources some of which are likely to be highly relevant to our understanding of host-microbe interactions. The International Human Microbiome Consortium aims to give an unprecedented view of the gut microbiota and validate microbial signatures of prognostic and diagnostic value. These approaches promise to identify the most redundant genomic traits of the human intestinal microbiota, thereby identifying the functional balance of this organ. Ultimately it will support the concept of a functional core within the intestinal microbiome. Reference(s) [1] Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh S, Nielsen T, Pons N, Levenez F, Yamada T, Mende D, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto J-M, Hansen T, Le Paslier D, Linneberg A, Bjørn Nielsen H, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Zhang X, Li S, Yang H, Wang J, Brunak S, Dor´ e J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. 2010. A human gut microbial gene catalog established by deep metagenomic sequencing. Nature In Press. [2] Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet J-P, Ugarte E, Mu˜ noz-Tamayo R, Le Paslier D, Nalin R, Dore J, Leclerc M. 2009. Towards the human intestinal microbiota. phylogenetic core. Environmental Microbiology. [3] Sokol H, Pigneur B, Watterlot L, Lakhdari O, BermudezHumaran LG, Gratadoux J-J, Blugeon S, Bridonneau C, Furet J-P, Corthier G, Grangette C, Vasquez N, Pochart Ph, Trugnan G, Thomas G, Blotti` ere HM, Dor´ e J, Marteau P, Seksik P, Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn’s disease patients. Proceedings of the National Academy of Sciences of the United States of America. 2008. E07 Gut microbiota and metabolism at the cross-road between homeostasis and chronic inflammation D. Haller. Chair for Biofunctionality, ZIEL Research Center for Nutrition and Food Science, CDD Center for Diet and Disease, Technische Universit¨ at M¨ unchen, Freising, Germany Lifestyle changes in the industrialized world are associated with a sharp increase in the incidence of chronically degenerative pathologic processes. The hallmark for the development of these chronically degenerative and “lifestyle-dependent” diseases of the modern world implies a complex interaction of genetic predispositions and environmental triggers. Nutritionrelated factors and the high caloric intake (over nutrition) together with components of the gut-associated microbial ecosystem (gut microbiota) emerge as prime environmental triggers for the development and modification of lifestylerelated chronic diseases such as chronic inflammatory disorders of the gastro-intestinal tract as well as metabolic pathologies such as obesity-associated insulin resistance and type 2 diabetes. Epidemiological analysis identified high fat diets to be associated with the progression of obesity-associated comorbidities and/or pathologies [1]. These correlations either