Today metabolomic approaches are aiming at the quest for homeostatic balance which is dependent not only on the host but also on the crucial metabolic interactions with microbial symbionts. Indeed, metabolomics technologies are broadening our knowledge on the roles of the human gut microbiota and how they influence health and disease etiology. While the mechanisms of action of our gut symbionts are only now being unveiled, potential health benefits are being suggested by modulating the microbial functional ecology with the use of probiotics. This chapter discusses latest metabolomics applications to explore mammalian gut microbial metabolic interactions with key emphasis on deciphering bacterial role in maintaining host health balance, as well as preventing and treating metabolic disorders.