Periodic Reporting for period 1 - METABIONT (Dissection of the host-microbe crosstalk that controls metabolism and physiology in intestinal symbiosis)
Berichtszeitraum: 2023-06-01 bis 2025-11-30
Our gut is home to trillions of bacteria that affect every aspect of our lives. A major goal of biomedical research is to understand how shifts in these microbial communities, called microbiomes, can provoke disease. This quest faces significant challenges, as there are fundamental aspects of host-microbiome interactions that we still do not understand. For example, gut bacteria can influence animal physiology by producing specific metabolites. Yet, for most of these molecules, we cannot predict their mode of action nor their effects. In parallel, a same bacterium can inhabit different sections of the gastrointestinal tract, which can represent vastly different habitats. Therefore, it is likely that a same bacterium can produce different factors depending of where it lives in the digestive system, but these spatial regulations remain elusive. The ERC project METABIONT will address these knowledge gaps by determining how animals and their symbiotic microbes influence each-other, thereby contributing to a better understanding of how microbiomes shape health and disease.
METABIONT will exploit the experimental tractability of the fruit fly Drosophila and model gut bacteria to answer these questions. The Drosophila gastrointestinal tract is similar in terms of anatomy, physiology and function to that of mammals. It harbors a simple microbiota, and some of its symbionts are also found in the mammalian digestive tract. Drosophila can also easily be maintained germ-free, which is advantageous for gnotobiology, the study of animals with a controlled microbiome. Using different gnotobiotic models, the ERC project METABIONT will investigate how bacteria adjust their physiology and metabolism along the digestive system to adapt to intestinal life (Research Aim 1). It will determine how bacterial factors subsequently shape intestinal metabolism and function (Research Aim 2). Finally, investigations will tie host and microbes together, and determine how both partners cooperate to fill each other’s nutritional needs (Research Aim 3).
In summary, This ERC project will investigate the molecular crosstalk between animals and their gut bacteria and its impact on metabolism and physiology at the scale of the holobiont, the biological entity composed of a multicellular organism and its symbiotic microbes. The project will address significant gaps in our understanding of intestinal mutualism, and expand our perspective on the role of the microbiome in animal health and disease.
METABIONT will exploit the experimental tractability of the fruit fly Drosophila and model gut bacteria to answer these questions. The Drosophila gastrointestinal tract is similar in terms of anatomy, physiology and function to that of mammals. It harbors a simple microbiota, and some of its symbionts are also found in the mammalian digestive tract. Drosophila can also easily be maintained germ-free, which is advantageous for gnotobiology, the study of animals with a controlled microbiome. Using different gnotobiotic models, the ERC project METABIONT will investigate how bacteria adjust their physiology and metabolism along the digestive system to adapt to intestinal life (Research Aim 1). It will determine how bacterial factors subsequently shape intestinal metabolism and function (Research Aim 2). Finally, investigations will tie host and microbes together, and determine how both partners cooperate to fill each other’s nutritional needs (Research Aim 3).
In summary, This ERC project will investigate the molecular crosstalk between animals and their gut bacteria and its impact on metabolism and physiology at the scale of the holobiont, the biological entity composed of a multicellular organism and its symbiotic microbes. The project will address significant gaps in our understanding of intestinal mutualism, and expand our perspective on the role of the microbiome in animal health and disease.
We have established robust protocols combining the use of gnotobiotic models with imaging, multi-omics approaches (RNA-seq, microbiome profiling, metabolomics, lipidomics, etc.) and innovative physiological assays to dissect the metabolic crosstalk between animals and their gut bacteria. These approaches have led to several discoveries, some of which have already been published and are fully accessible to the public. Notably, we have discovered that microorganisms can act though epithelial bacterial sensing to influence essential metabolic functions in the gut, such as digestion. We have discovered that in return, specific host metabolic pathways shape bacterial density and diversity in the intestine. Finally, we investigate how bacteria communicate with their hosts to influence transit. Transit is the controlled passage of food through the digestive system, and this vital function has a profound impact on the nutrition of both animals and their symbiotic bacteria. We have discovered the genetic support for these regulations, and are currently investigating how transit speed influences physiology in the holobiont.
Our multidisciplinary project takes a three-pronged approach to investigating host-microbiome interactions, by considering the perspective of the microbe, the host, and the holobiont. As such, METABIONT covers essential aspects of intestinal mutualism and has already produced several unanticipated findings. The project may therefore push the field of microbiome research in new directions, offering new insights into how gut bacteria influence animal health and disease.