SILVESTRI, ALESSANDRA
A GUT PATCH FOR OBESITY - SUPERABSORBENT HYDROGEL AS A NOVEL THERAPEUTIC INTERVENTION [Tesi di dottorato]
Università degli Studi di Milano, 2020-12-11

The intestinal barrier is the first line of defense against pathogens that separates our body from the external environment. Its function is to maintain intestinal tissue homeostasis, regulating the passage of molecules and protecting from harmful microbes. This barrier is made up by the mucus layer, critical for limiting the exposure to the gut microbiota, and by intestinal epithelial cells sealed by inter-epithelial tight junctions. A strong cause-effect relation between intestinal permeability alterations and both intestinal and systemic diseases (obesity, type 2 diabetes and NAFLD) is becoming evident, suggesting that restoring proper gut permeability by targeting the intestinal epithelial barrier could represent a successful intervention. The present study proposes the use of a naturally-derived superabsorbent hydrogel to restore gut permeability, likely acting on the intestinal epithelial barrier, either directly or indirectly. In a mouse model of HFD-induced obesity, hydrogel diet supplementation prevented early development of adiposity, hepatic steatosis and intestinal barrier perturbations, mainly reinforcing intestinal epithelial TJ and inhibiting bacterial LPS translocation and endotoxemia. In long-term HFD experiments, both prophylactic and therapeutic hydrogel administration reduced body weight, adipose tissue deposition and improved metabolic parameters; notably, this was paralleled by the restoration of intestinal barrier permeability, thus limiting endotoxemia, as well as the reshaping of the gut microbiota composition despite dysbiosis associated to HFD feeding. Indeed, both dysbiosis and low-grade inflammation are hallmarks of metabolic diseases. Collectively our data show the potentiality of this superabsorbent hydrogel as a completely naturally-derived and non-invasive therapeutic tool for the treatment of obesity and metabolic disorders.

diritti: info:eu-repo/semantics/embargoedAccess
In relazione con info:eu-repo/semantics/altIdentifier/hdl/2434/789297
ALCALAY, MYRIAM
tutor: M. Alcalay ; co-tutor: M. Rescigno ; internal advisor: D. Pasini ; external advisor: A. Sannino ; coordinator: G. Viale
VIALE, GIUSEPPE
Settore MED/04 - - Patologia Generale


Tesi di dottorato. | Lingua: Inglese. | Paese: | BID: TD21001674