Gut micro-organisms are recognized as crucial regulators of host immunity and the microbiota has been implicated in several inflammatory, immune, inflammatory or even psychiatric disorders. Therefore the analysis of the complex interactions between gut microbiota and the host is currently under intense investigation. Most of our knowledge stems from the study of animal models while translational research and data in humans are necessary to move the field forward and to evolve to diagnostic and therapeutic application. Amongst the microbial by-products, short chain fatty acids such as acetate yielded by fermentation of non-digestible fibers, were pointed as metabolic modulators. Here we highlight a study evaluating the effects of colonic infusion of one of the short chain fatty acids, acetate, in a cohort of overweight and obese normoglycaemic subjects.