Descripción del proyecto
Desvelar la relación entra la microbiota intestinal y el hospedador
Los microorganismos intestinales, conocidos en conjunto como flora intestinal, desempeñan una función esencial en la salud humana: producen moléculas bioactivas y metabolitos que influyen en el metabolismo del hospedador y su expresión génica. Para dilucidar por completo las interacciones metabólicas precisas que tienen lugar entre la microbiota y el hospedador, se requieren métodos que discriminen entre los metabolitos generados por el hospedador y por los microorganismos. A fin de abordar estas limitaciones, el equipo del proyecto GutTransForm, financiado por el Consejo Europeo de Investigación, se propone desarrollar un método sistemático que utilice moléculas de fármacos para investigar la capacidad de la microbiota intestinal para modificar sustancias químicas. Este método ayudará a revelar aspectos básicos de la relación entre la microbiota y el hospedador que podrían ser útiles en el diseño de tratamientos médicos.
Objetivo
The variability of the human gut microbiome (entirety of microorganisms inhabiting the intestine) far exceeds human genome variability, and has been connected to various aspects of human health. Although microbiome differences are often linked to altered metabolism, the current view on metabolic interactions between the microbiota and the host remain mostly descriptive due to several limiting factors. First, most sequencing-based human microbiome studies rely on correlative analyses between microbiome composition and human phenotypes, depend on largely incomplete microbial genome annotations, and are not targeted to identify community-mediated functional traits. Second, many metabolites can be both of microbial and human origin, which makes it conceptually and methodologically challenging to disentangle metabolic microbiota-host interactions.
To overcome these limitations, I propose a systematic bottom-up strategy to mechanistically study metabolic microbiota-host interactions by harnessing gut microbiota’s capacity to biotransform (chemically modify) drug molecules. The large chemical diversity and exogenous origin makes medical drugs ideally suited for experimental in vitro and in vivo approaches to probe microbiota-host interactions in a controlled way. We will combine high-throughput culturing protocols, genetics, metabolomics measurements, genomics analyses, gnotobiotic mouse work, and computational modeling to connect interpersonal differences in microbiome composition to differences in metabolic functions of individuals’ gut microbiota, and ultimately link them to molecular host phenotypes. Generating these mechanistic insights and transformational resources is essential to understand the fundamental principles of the microbiota-host relationship. In addition, this project has direct medical relevance, as it provides actionable microbiome-based links to interpersonal differences in medical drug response, which remain a widespread problem in clinical practice.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
ERC - Support for frontier research (ERC)Institución de acogida
69117 Heidelberg
Alemania