Each individual can be distinguished by the heterogeneity of the trillions of microbes inhabiting his gastrointestinal tract. This concept, together with the role that gut microbiota is considered to play in the induction of metabolic diseases, paves the way for the development of personalized medicine. By exploiting our unique animal model of metabolic adaptation to a high-fat diet, we have recently shown that differential gut microbiota lead to different metabolic phenotypes—metabotypes. Moreover, we have also reported that a given metabotype can be distinguished by different profiles of gut microbes, symptomatic of the complexity of the regulation of host physiology by gut microbiota. Furthermore, in an effort to find bacterial predictors of type 2 diabetes (T2D), we discovered that in a healthy population, subjects who subsequently developed T2D had increased blood levels of bacterial 16S rDNA well before. In addition, tissue (blood) microbiota, mainly characterized by Proteobacteria (up to 90%), has been discovered both in healthy individuals and in diabetic patients. Altogether, our results confirm the presence of gut microbes and propose tissue microbiota as new targets for the innovative treatment of T2D.