The prevalence of obesity is continuously growing and has reached epidemic proportions. It is clear that current methods to combat obesity are not effective enough to reduce the problem. Therefore, further investigation is needed to develop new strategies. Recent research pointed out a potential role of the microbial community associated to the human host in controlling and influencing the energy homeostasis. According to the concept of Gastrointestinal Resource Management, this microbiota and its metabolic potential can be steered with the aim of improving host health. This review therefore focuses on the modulation of the intestinal microbiota through prebiotics with the aim to control of several aspects of metabolic homeostasis. In a first part, the importance of host-microbe cross-talk at the intestinal epithelium is discussed. Yet, energy metabolism, which includes both lipid and glucose metabolism, is also regulated by several key organs including the adipose tissue, brain, liver, muscles, pancreas and gut. Therefore, in a second part, we will discuss the microbial factors that are involved in the communication between these different tissues, and their potential management. Finally, we will give some future prospects of the use of prebiotics in an individualized treatment of metabolic disorders.