Innovative Approach to Fecal Microbiota Transplantation (FMT) Applied for Chronic Kidney Disease (CKD)

The aim of this PhD project focuses on the relationship between intestinal microbiota and health in the background of Chronic Kidney Disease (CKD). Many pathologies, including the CKD, display a dysbiosis of the intestinal microbiota, which is at the same time a consequence of CKD and contributes to its progression and complication. In a variety of chronic-degenerative and infectious diseases, the "fecal microbiota transplantation" (FMT) is being tested in recent years in addition with the application of both probiotics and prebiotics. FMT is indeed currently successfully used in the eradication of recurrent Clostridium difficile infections, with success rates of 90%, thus recent evidence suggests that FMT could be applied in other diseases characterized by microbiota dysbiosis, such as CKD and diabetes, in which the FMT has never been previously tested. This project will allow to study: i) the prototypal production of the encapsulated suspension of healthy microbiota tested in a minimally invasive FMT procedure (by oral administration); ii) the efficacy of the innovative prototype for colonization and modulation of intestinal microbiota following FMT; iii) the experimental and clinical feedback of this suspension, by in vivo studies.

This project will allow to experiment the Fecal microbiota transplantation in the CKD model and to set up a pharmaceutical formulation of fecal suspensions of microbiota. Firstly, a collection of fecal samples from healthy volunteers will be set up, with the aim to collect biological samples. Screening and enrollment of healthy volunteers, gathering personal and clinical information together with eating habits, will be performed. The best product design in efficacy, stability over time as well as suitable excipients and any other active components able to perform a synergistic action will be evaluated. After defining the pharmaceutical formulation, the production of the prototype will be finalized. In a second time in vivo studies on a model of CKD (uremic mouse with CKD induced by 5/6 nephrectomy) will be designed and carried on. The CKD model will be used to evaluate the effects and the outcomes of FMT on clinical parameters such as renal function, circulating levels of uremic toxins, state and function of the intestinal microbiota, intestinal permeability and microbiota composition. This step will be necessary to establish the efficacy of the innovative prototype for the colonization and the modulation of intestinal microbiota following FMT.