PIF2024-NEOGUT- MICROAMBIENTE INTESTINAL NEONATAL: EL PAPEL DE LOS ENTEROCITOS VACUOLADOS EN LA COMUNICACION INTESTINAL, LA HOMEOSTASIS Y LAS ENFERMEDADES-PID2023-151844OB-I00

The intestine is one of the central organs of the body: it controls the host's metabolism and physiology and presents a critical function of immunity through the constant interaction with commensal microbes and pathogens. This interaction is essential for obtaining its functional balance, known as intestinal homeostasis. Intestinal homeostasis is consolidated throughout the individual's life but must be established at birth when exposed to microbes. The immune system must balance protecting the newborn from pathogens while ensuring tolerance to beneficial microbes that are critical for health. Alterations of gut homeostasis can lead to the development of chronic inflammatory diseases such as IBD and colorectal cancer (CRC). However, the influence of the neonatal microenvironment to them is unknown. Our recent results have demonstrated that NEs have a very high metabolic activity that largely depends on their enormous autophagic activity and a conspicuous mitochondrial network. We hypothesize that the function of the NEs must be essential for establishing intestinal homeostasis, not only at the neonatal stages, but also in adults. This function must be modulated by the mitochondrial-lysosomal activity of NEs, establishing a metabolic communication regulating the microbiota and mucosal immune system. The goal of NEOGUT proposal is to characterize the importance of neonatal NEs for establishing intestinal homeostasis and their importance in developing IBD and CRC.