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The gut microbiota is now widely recognized as an important factor contributing to the regulation of host metabolic functions. Numerous studies describe an imbalance in the gut microbial ecosystem in response to an energy-dense diet that drives the development of metabolic disorders. In this context, the manipulation of the gut microbiota by food components acting as prebiotics appears as a promising strategy. Several studies have already investigated the beneficial potency of prebiotics, mostly inulin-type fructans, on host metabolism and key intestinal functions including gut hormone release. For the last 20 years, several non-digestible compounds present in food have been shown to modulate the gut microbiota and influence host metabolism in essential organs involved in the control of energy homeostasis. To date, numerous reviews summarize the impact of prebiotics on the liver or the brain. Here we propose to describe the mechanisms by which prebiotics, through modulation of the gut microbiota and endocrine functions, modulates the metabolic cross-talk communication between the gut, the adipose tissue and skeletal muscles.