Thomas Clavel Microbiologist Thomas Clavel Microbiologist Gut microbiome in health and diseases: From ecosystem description to functional studies Gut microbiome in health and diseases: From ecosystem description to functional studies Habilitation - 2014 Habilitation - 2014 Gut microbiome in health and diseases: From ecosystem description to functional studies Habilitationsschrift vorgelegt von Dr. rer. nat. Thomas Clavel Nachwuchsgruppe Intestinales Mikrobiom Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL) Lehrstuhl für Ernährung und Immunologie Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt Freising-Weihenstephan Technische Universität München 2014 Acknowledgements For me, science is curiosity and the wish to understand and discover. But, most of all, science is made by human beings. Hence, one major driving factor in science is the exchange of knowledge, ideas, opinions, and emotions (which can be sometimes unfortunate if emotions are too negative, ignored or not under control). Many individuals in and outside scientific communities have influenced my career to date, and in many different ways. Due to space limitation and the fear to forget anyone, I will not draw here an exhaustive list. I will name just a few, knowing that all the persons who know me and have accompanied me on this journey will recognize themselves when reading these lines. Over the last twelve years, I have had the privilege to be mentored by three outstanding scientists: Dr. Joël Doré, Prof. Michael Blaut, and Prof. Dirk Haller. In my opinion, they are outstanding for different reasons, and I am very grateful to have had the chance to learn from each of them. Joël, thanks to your wise guidance and your kindness, you have been a model in early steps of my career and throughout thereafter; thank you! Michael, your unconditional support, and your sense of loyalty and accurateness are exemplary: thank you! Dirk, your exhaustless dynamism, your clarity of vision, and your determination have always been very inspiring; thank you! As already said, there are far too many names to be quoted here. I wish to express my gratitude to all professors, faculty members, colleagues and friends in Jouy, Potsdam, and Freising, who have supported me with my research and far beyond! I am also thankful to the colleagues and friends from partner institutions for fruitful exchanges and for making research so enjoyable. My life, and thus my research, finds its source in all my friends, my family, and Julia: Thanks for all the shared moments, love, energy, and for showing me ways I would not have explored. Table of contents Prelude ....................................................................................................................... 5 Curriculum vitae .......................................................................................................... 6 List of publications ...................................................................................................... 7 Summary .................................................................................................................. 11 Zusammenfassung ................................................................................................... 12 Résumé .................................................................................................................... 13 PART I .............................................................................................................. 14 Chapter 1 - Introduction ......................................................................................... 14 1 Background information ................................................................................. 14 2 Questions and objectives ............................................................................... 19 Chapter 2 - Main research activities and achievements ..................................... 20 1 Microbiota diversity ........................................................................................ 21 1.1 Culturing is worth the effort ...................................................................... 22 1.2 The need for molecular studies................................................................ 27 2 Nutrition and microbiome ............................................................................... 33 3 Microbe-host interaction: The gut-liver axis .................................................... 39 Chapter 3 - Conclusion .......................................................................................... 43 Cited literature .......................................................................................................... 44 PART II ............................................................................................................. 50 Selected publications ................................................................................................ 50 Prelude The present manuscript summarizes the outputs of my research activities in the field of gut microbial ecology since the official start of my Habilitation in May 2010. It is a cumulative work based on scientific papers published within the last 4 years. There should be no need of saying this, but as the rewards of collaborative effort in science get sometimes lost, I wish to make this clear from the start: I have been the major driver of the research outputs presented throughout the text, but I received of course intellectual, technical and infrastructural input from mentors, colleagues, team members in my junior group, and external collaborators, most of whom appear in the author lists of selected publications. Part I of this Habilitation manuscript is divided into three chapters that respectively introduces some key concepts in the field, summarizes results, and gives some perspectives. Chapter 2 (the presentation of results and my research strategy) is the core of part I and is also divided into three sections according to my main research interests: (1) Microbiota diversity; (2) Nutrition and microbiome; and (3) Microbe-Host interaction. For the sake of clarity, each page of these sections is marked with the appropriate number (1, 2 or 3) in the right margin. In each of these three sections, I not only present major findings of my research on the corresponding topic, I also explain the rationale behind the work, detail some major accomplishments, and give opinions. That is, the present manuscript can be considered as the foundation of my research in the next few years. Part II is the compilation of peer-reviewed original work published in scientific journals or as book chapters, which make up the backbone of part I. These publications are sorted as well into the three sections (1) “Microbiota diversity”, (2) “Nutrition and microbiome”, and (3) “Microbe-host interaction”. As in part I, for the sake of clarity, each page of these papers is numbered in the right margin according to the section to which the given publication belongs. 5 Curriculum vitae Dr. rer. nat Thomas Clavel Born on October 6th 1978 in Toulon (France) RESEARCH ACTIVITIES: Present Junior Research Group Leader - Intestinal Microbiome (TUM, ZIEL) 2006-2011 Postdoctoral Research Associate; Dirk Haller’s lab (TUM) 2002-2006 German-French joint PhD project; Michael Blaut’s lab (DIfE) 2002 Master project; Joël Doré’s lab (INRA) ACADEMIC QUALIFICATIONS: Present Ongoing habilitation (TUM) Feb 2006 PhD in microbiology (University of Potsdam and Châtenay-Malabry) Sept 2002 M.Sc. in Agricultural Sciences and Human Nutrition (ENSAR) May 1999 B.Sc. in biology (University of Toulouse) July 1997 French Scientific Baccalaureate (specialised in Mathematics) AWARDS: Apr 2013 Grant holder of the European Nutrition Leadership program (advanced) July 2009 Travel awards (DAAD, SMI) May 2009 Travel awards (Danone Institute and SGM) Sept 2008 Stipend for research visits (BFHZ and SGM) June 2007 1st price for excellent PhD (University of Châtenay-Malabry) Apr 2006 Travel grant (SGM) Oct 2004 Scholarship holder of the DAAD Academic Exchange Service 6 List of publications Total number published: 29; citations: ca. 1260; cumulative impact factor: ca. 140; h-index: 16 Peer-reviewed original work as principal investigator: 1. T Clavel,* C. Desmarchelier, D Haller, P Gérard, S Rohn, P Lepage, H Daniel (2014) Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance, Gut Microbes 5:544 (IF = 2.2); (* corresponding author) 2. H Daniel, A Moghaddas Gholami, D Berry, C Desmarchelier, H Hahne, G Loh, S Mondot, P Lepage, M Rothballer, A Walker, C Böhm, M Wenning, M Wagner, M Blaut, P Schmitt-Kopplin, B Kuster, D Haller, T Clavel (2014) High-fat diet alters gut microbiota physiology in mice, ISME J 8:295 (IF = 9.0; 14 citations) 3. K Kläring, L Hanske, N Bui, C Charrier, M Blaut, D Haller, CM Plugge, T Clavel (2013) Intestinimonas butyriciproducens gen. nov., sp. nov., a novel butyrate-producing bacterium from the mouse intestine, Int J Syst Evol Microbiol 63:4606 (IF = 2.1) 4. T Clavel,* C Charrier, M Wenning, D Haller (2013) Parvibacter caecicola gen. nov., sp. nov., a new bacterium of the family Coriobacteriaceae isolated from the caecum of a mouse, Int J Syst Evol Microbiol 63:2642 (IF = 2.1); (* corresponding author) 5. T Clavel,* C Charrier, D Haller (2013) Streptococcus danieliae sp. nov., a novel bacterium from the caecum of a mouse, Arch Microbiol 195:43 (IF = 2.1; 3 citations); (* corresponding