Bile acids as determinants of postprandial metabolism and intestinal microbial colonization in newborns

Abstract

Bile acids (BA) are amphipathic compounds produced by the liver that participate in the emulsification of dietary lipids. Due to the nature of the enterohepatic circulation and the partial escape of these molecules from first-pass absorption by the liver, plasma concentration of BA increases up to 20-fold after the ingestion of a meal, similarly to what occurs with certain hormones. In the last two decades, the identification of membrane receptors and transcription factors activated by BA, aroused interest for their effects as compounds involved in cell signaling processes.The present proposal is divided into 3 subprojects focused on investigating the metabolism and biological function of BA: a) the first study will aim to investigate the relationship between postprandial increase of BA with metabolic and inflammatory changes that occur after the ingestion of a meal; b) the second study will focus on the relationship between the presence of BA in milk and the establishment of the intestinal microbiota of newborns. Due to the antimicrobial character of BA, these molecules are among the main regulators of the intestinal microbiota composition. Despite having already been described in the 1980s, the presence of BA in milk is little known and no study has been dedicated to investigating this relationship, probably because the analytical tools that allow this in-depth assessment have only been developed in the last decade. c) a third study will focus on the characterization of an animal model to investigate metabolic and inflammatory changes in different tissues triggered by the ingestion of a meal. Such a model will be of great value for research in the area and will allow exploring the relationship between the postprandial increase of BA in plasma with the metabolic changes observed in the postprandial period.The present proposal is innovative and has the collaboration of several renowned researchers, both in Brazil and in other countries. These researchers will contribute to the collection and analysis of samples and will be able to receive graduate students on international internships. We have identified challenges to the execution of the project, but we have already anticipated measures to overcome them, and we foresee the recruitment of graduate and undergraduate students and a technical training intern to form the team executing the project. We are excited about the possibility of testing the formulated hypotheses, certain that the results will contribute to the advancement of the area. (AU)