Antibiotics treatment promotes vasculogenesis in the brain of glioma-bearing mice
Maria Rosito, Javeria Maqbool, A. Reccagni, Ottavia Giampaoli, Fabio Sciubba, Fabrizio Antonangeli, Ferdinando Scavizzi, Marcello Raspa, Federica Cordella, Lucrezia Tondo, Silvia Di Angelantonio, Flavia Trettel, Alfredo Miccheli, Giuseppina D’Alessandro, Cristina Limatola
Abstract
In recent years, several studies described the close relationship between the composition of gut microbiota and brain functions, highlighting the importance of gut-derived metabolites in mediating neuronal and glial cells cross-talk in physiological and pathological condition. Gut dysbiosis may affects cerebral tumors growth and progression, but the specific metabolites involved in this modulation have not been identified yet. Using a syngeneic mouse model of glioma, we have investigated the role of dysbiosis induced by the administration of non-absorbable antibiotics on mouse metabolome and on tumor microenvironment. We report that antibiotics treatment induced: (1) alteration of the gut and brain metabolome profiles; (2) modeling of tumor microenvironment toward a pro-angiogenic phenotype in which microglia and glioma cells are actively involved; (3) increased glioma stemness; (4) trans-differentiation of glioma cells into endothelial precursor cells, thus increasing vasculogenesis. We propose glycine as a metabolite that, in ABX-induced dysbiosis, shapes brain microenvironment and contributes to glioma growth and progression.