The gut microflora can be considered a metabolically active organ composed of a vast and complex community of microorganisms that has an important role in the stability and functional activity of the intestinal ecosystem. Recently, thanks to microarray technology, a global screening of the microflora's regulated genes has allowed the analysis of the complex bacteria-host interplay. In particular, most of our knowledge comes from studies on Bacteroides thetaiotaomicron, a prominent member of the intestinal microflora of mice and humans. The results of published studies have revealed that Bacteroides thetaiotaomicron modulate the expression of a large quantity of genes implicated in different aspect of host physiology. This review aims to illustrate the specific contributions of this intestinal microorganism in three important aspects of host physiology: mucosal barrier reinforcement, immune system modulation and nutrients metabolism. In particular, we focus on recent insights about the molecular mechanisms by which Bacteroides thetaiotaomicron help the host in these important functions.