Characterization of the inulin effects on microbiota and hypoxia and its relationship with HIF-1a stabilization in the colon of mice

Abstract

Soluble fibers act by modulating the composition and metabolism of the intestinal microbiota, which, in turn, influences the metabolites profile produced and biological interactions with the host. Microbiota metabolites regulate energy metabolism genes and stimulate the luminal oxygen consumption, triggering a hypoxia response which is dependent of HIF-1a stabilization. Multiple studies indicate a significant role of high fiber diets in maintaining a healthy microbiota and in HIF-1a stabilization in IECs. However, the physiological impact of fibers on HIF-1a stabilization in the colonic epithelium is poorly understood. Moreover, the influence of soluble fiber on the microbiota composition and produced metabolites has not been widely characterized. Therefore, in this project, we propose to investigate the effects of inulin - a type of soluble fiber - on the microbiota profile and intestinal hypoxia and its relationship with HIF-1a stabilization in the colon of mice. Furthermore, we intend to clarify whether these effects of inulin are related to the cell proliferation control exerted by HIF-1a stabilization in the colonic epithelium. The data generated by this project, will allow us to understand the contribution of inulin and HIF-1a stabilization to the maintenance of epithelium homeostasis. Additionally, the findings may provide insights to understand how pathological processes are stablished in the intestinal epithelium. (AU)