Impact of Proanthocyanidins on Intestinal Dysfunction Induced by Nutritional or Chemical Agents

Identificador:  TDX:3103

Handle: https://hdl.handle.net/20.500.11797/TDX3103

Autors:  González Quilen, Carlos Alberto

Resum:
The intestinal tract is a site of interaction with microorganisms and potentially detrimental environmental factors. The high intake of fructose and saturated fats typical of the Western diet has been associated with intestinal dysfunction (disruption of barrier function and inflammation) and an increased influx of proinflammatory bacterial endotoxins into the systemic circulation. In turn, high concentrations of plasma endotoxins (metabolic endotoxemia) are a precursor to the onset of metabolic syndrome. In view of the above, the intestine is emerging as a target for disease prevention and therapy. Proanthocyanins (PACs) are naturally occurring phenolic compounds with remarkable anti-inflammatory properties in the intestinal mucosa, according to preclinical studies. Thus, PAC administration is a promising adjunctive therapeutic strategy for the treatment of intestinal dysfunction, but its efficacy in humans is yet to be confirmed. The main objective of this doctoral thesis was to evaluate the impact of a grape-seed PAC extract (GSPE) on a rat and cell culture-based model of intestinal dysfunction and to investigate its effectiveness in humans. We found that a long-term Western-style diet (cafeteria diet) induces intestinal dysfunction in rats, and that alterations in the permeability of the colon largely contribute to metabolic endotoxemia. These effects are partially driven by high luminal concentrations of fructose and could be effectively reversed in vivo by pharmacological doses of GSPE. Lastly, we compared these findings with evidence derived from an ex vivo human model of chemically-induced colonic dysfunction in which we were able to replicate the reduction of intestinal permeability and the amelioration of inflammatory status by means of GSPE found in vivo. In conclusion, the administration of GSPE results in the overall improvement of intestinal dysfunction and associated metabolic endotoxemia. Effective doses in humans are probably pharmacological and will have to be determined in clinical trials.