Physiologie intégrative : nutrition, métabolisme et microbiote / Integrative physiology: nutrition, metabolism and microbiota

Séminaire FSER organisé par François Leulier (Institut de Génomique Fonctionnelle de Lyon, France)
du 25 au 30 avril 2016
Interconnexions fonctionnelles entre l’environnement microbien et l’environnement nutritionnel des organismes multicellulaires et leurs implications.

Participants

Martin Blaser, Patrice Cani, Maria Dominguez-Bello, Michael Hall, Martin Holzenberger, Gerard Karsenty, Won-Jae Lee, Pierre Leopold, François Leulier, Lesley Macneil, Irene Miguel-Aliaga, Gilles Mithieux, John F. Rawls, Martin Schwarzer, Stephen Simpson, Bernard Thorens, Carl Thummel, Hubert Vidal, Lipin Zhao, Anne Granger (Cell Metabolism – Cell Press) and Héloïse Dufour (Cercle FSER)

Résumé

Le séminaire « Physiologie intégrative: à la croisée de la nutrition, du microbiote, de la croissance et du métabolisme » s’est tenu fin Avril 2016 au Domaine de la Fondation des Treilles. Il a réuni dix-huit biologistes de renommée internationale, un jeune chercheur et une journaliste, venus principalement d’Europe mais aussi des Etats-Unis, du Canada, de Corée du Sud, de Chine et d’Australie. L’objectif de ce séminaire était de discuter les interconnections émergeantes et les liens d’interdépendance entre les thématiques scientifiques que sont la nutrition, l’étude du microbiote et la physiologie en axant la réflexion sur la croissance juvénile et le métabolisme adulte. L’une des ambitions du séminaire était d’illustrer et de faire émerger la jeune discipline qu’est la physiologie intégrative dont le sujet d’étude porte justement sur ces liens d’interdépendances entre ces thématiques de recherche connexes. Dans ce but, nous avons réuni des experts de ces différentes disciplines travaillant avec des organismes animaux modèles diversifiés. La moitié des participants travaillent directement sur des thématiques de recherches liées aux interactions entre microbiote et physiologie tandis que l’autre partie des participants focalisent leur travaux sur la nutrition et ou la physiologie. Nous avons souhaité ce mélange d’expertises afin de favoriser la curiosité et les échanges scientifiques lors du séminaire ; de plus, la succession des présentations avait été organisée de manière à assurer le meilleur mélange des thématiques. Tous les participants ont présenté leur travaux passés et leurs dernières découvertes, souvent non publiées, et nous avons formalisé les échanges, idées, concepts et conclusions ayant émergé pendant le séminaire lors d’une session de discussion finale modérée par notre participante journaliste. Le compte-rendu de cette session devrait faire l’objet d’une publication dans un journal scientifique à forte visibilité dans les mois à venir.

Abstract

The meeting “Integrative physiology: at the crossroads of nutrition, microbiota, growth and metabolism” gathered 19 biologists (Ph’D and MD/Ph’D) and one journalist (the senior scientific editor of the Cell Press journal Cell Metabolism) coming from around the world (mostly Europe but also US, Canada, South Korea, China, Autralia). The meeting took place late April 2016 in the wonderful “Domaine des Treilles”, a venue ideal for such small meetings, relaxing and inspiring enough to give participants all the serenity they need to stimulate fruitful discussions.

The scientific scope of the meeting was to discuss the emerging links and interdependence among the topics of nutrition, microbiota, growth and metabolism. We coined these topics under the umbrella term “integrative physiology”.

Review

The participants were a mix of internationally renowned scientific leaders, several established group leaders, a few young group leaders and a young researcher. We are experts from these four different fields and use a diverse array of models organisms, including longitudinal and clinical human studies. Each participant gave a seminar presenting his/her work. Half of the participants study host/microbiota interactions while the other half work on nutrition/physiology-centered topics without a particular focus on the microbiota. Talks from each topic were intertwined in the agenda and this mixture fostered interest, discussion and collaborative brainstorming.

The “microbiota and physiology” topic covered: The ancient and the early microbiome (M.G. Dominguez-Bello); the impact of antibiotics on metabolic parameters through microbiota changes (M. Blaser); the use of prebiotics to manage the impact of microbiota on metabolic diseases (P. Cani); the contribution of the gut microbiota to human metabolic phenotypes (L. Zhao); the microbiota-produced metabolites and their impact on gut-brain neural signalling (G. Mithieux); the impact of microbiota on vertebrate nutrition, physiology and energy balance (J. Rawls); the influence of microbiota on C.elegans health (L. McNeil); the gut microbiota as an environmental factor contributing to Drosophila immunity and development (W.J. Lee) and the host/microbiota interactions in Drosophila and mice upon chronic undernutrition (F. Leulier & M. Schwarzer).

The “Nutrition and Physiology” topic covered: the nutritional geometry of metabolic health (S. Simpson); the nutrient sensing mechanisms controlling systemic growth (P. Leopold); the Insulin-like growth factors linking environment to mammalian lifecycle and age-dependent disease (M. Holzengerger); the mTOR signalling in growth and metabolism (M. Hall); the cross-talk between bone and muscle during exercise (G. Karsenty); the gut-skeletal muscle axis in the control of metabolic homeostasis (H. Vidal); the impact of the gut-brain axis on physiology (I. Miguel-Aliaga); the brain glucose sensing cells in metabolic homeostasis and feeding behaviour (B. Thorens) and the transcriptional regulation of metabolism by nuclear receptor (C. Thummel).

The meeting ended by a general discussion chaired by Anne Granger, the Senior scientific editor at Cell Metabolism. We summed up the ideas, concepts, questions that arose during the meeting. I am currently working to synthesize these outputs into the format of a collaborative “perspective” paper to be published in Cell Metabolism late 2016 or early 2017. In brief, we discussed the influence of nutrition not only on the host but particularly on the microbiota itself and vice versa, i.e how microbiota influences host nutrition by modifying the dietary environment of the animals. The notion of long-term effects (during adult life and ageing) of early exposure to altered microbial environment (at birth or during infancy) was also illustrated and discussed. The importance of studying sex differences in phenotypes was also highlighted. During the meeting, we specified our vision of the term “integrative physiology”: which to us can be defined as an extension of the discipline of physiology that focuses on organ-to-organ communication and function, but research in integrative physiology aims to define and delineate such inter-organ communication and function in interaction with the nutritional and microbial environment of multicellular organisms. Even though in this meeting we focused on animal models, we believe this vision applies to all living organisms. A major axis of this meeting was to evaluate the different use of model organisms in studying integrative physiology. We reached the consensus that not all models were suitable for all biological questions, and we therefore emphasized the importance of choosing the adequate model organism to study a given biological question, and multiple models and approaches are healthy for a research field. Using animal models also allow the identification of conserved functional modules between organisms and therefore reveal the evolutionary roots of biological phenomena and mechanisms. It was clear to us that the research field studying the influence of microbiota on host physiology is young and impressive progresses have been made by phenomenological studies. Even though we acknowledged the value of sophisticated description of phenomena at the crossroads of disciplines without the ultimate necessity of going to mechanistical insights, there will be a need in the future to move from phenomena to mechanisms, where the use of model organisms will play a decisive role. Importantly, we acknowledged the fact that the microbiome seems a central pillar of biology, but investigators should be careful of not getting lost in its complexity. So far correlative studies have been too much taking the centre stage in the field, it is essential to move from correlation to causation and again model organisms will be instrumental to attain this objective. Finally, we briefly discussed several important topics that were not covered in the talks and were probably missing in this meeting. Examples include the influence of circadian rhythms on metabolism and microbiota, the epigenetic influence on metabolism, the new therapeutic options envisaged around intestinal microbiota in health and disease, and last but not least the strong ties between the intestinal microbiome, nutrition and host immunity. Interestingly it was mentioned that the influence of microbiome on the host, and vice versa is very evident in immunology, but far less in the metabolism and physiology fields, yet we can expect this notion of reciprocal influence between the microbiota and its host to be also applicable to metabolism and physiology hence opening exciting avenues of research.


A la suite de cette rencontre, publication en mars 2017 de l’article « Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health » dans la revue Cell Metabolism

Lors de ce séminaire a également été organisé par Héloïse Dufour, du Cercle FSER, le troisième « meeting scientifique ouvert au public ». Cette session, fortement appréciée par les participants du séminaire et les visiteurs du jour, a consisté en plusieurs rencontres brèves et informelles entre une cinquantaine d’élèves du secondaire d’un lycée proche des Treilles (Lycée Thomas Edison de Lorgues) répartis en petit groupe de 4/5 élèves et un ou une chercheur(e) participant au séminaire, l’objectif étant de favoriser les échanges entre scientifiques et le public afin de combler le fossé entre la science et la société et peut-être de faire émerger des vocations pour la Science chez ces jeunes élèves.