Bile salts play a vital role in regulating host homeostasis, acting as mediators in the complex and fine-tuned host-microbe crosstalk. By influencing bacterial load and composition, bile salts can modulate the intestinal ecology. In turn, resident bacteria modify bile salts thereby regulating the host’s response. Although crucial, the mechanistic understanding on this delicate and dynamic equilibrium is still elusive. In this context, we aim at expanding our knowledge on the host-bile-bacteria dialogue. This project will first focus on the identification and functional validation of key species within the gut microbiota, involved in bile metabolism, along with the impact of different bile salts on bacterial communities. For this, we will use microbial culturing techniques, bacterial amplicon sequencing and targeted metabolomic analysis. Ultimately we will establish a small intestinal model, coupled with a hepatocyte model to unravel the role of the bile-bacteria on intestinal, immune and hepatic cellular red-out. Overall, the outcome of this project will provide insights on how bile salts can be used to shape the gut microbiota but also how these microbial bile modifications elicit host responses that are essential in overall homeostasis.