text: Bacteria-host cell interactions is an area of growing interest. While pathogenic bacteria and their interaction with the human host traditionally received much attention, there is a growing interest for the beneficial role that non-pathogenic bacteria play at these interfaces and in the GI tract in particular. Growing number of studies indicate that intestinal bacteria influence host energy balance, immune responses and contribute to gut homeostasis, however the mechanisms underlying this dialogue still remains largely unexplored. The work presented in this thesis aims to review the present knowledge on bacteria-host interactions in the GI tract, and to demonstrate the importance of in silico analyses that are widely used in the modern era of genome sequencing to broaden our knowledge. It also shows how this information can be applied for functional studies aiming to decipher molecular mechanisms involved in bacteria-host interactions. The main results presented in this thesis can be divided into three parts. The first part deals with the development and validation of a new protein sequence analysis method to predict potentially surface exposed (PSE) proteins from Gram-positive bacteria. The second part describes the application of the newly developed prediction method to the proteomes of sequenced lactobacilli revealing important differences in their predicted surface protein content. Finally, in the third part we demonstrated how the application of the in silico tools may be applied for functional protein studies. In this part, we focus on the potential immune modulation effects of surface exposed proteins from Lactobacillus delbrueckii subsp. Bulgaricus ATCC 11842.