THE ROLE OF GLYCINE AS MEDIATOR OF GUT MICROBIOTA ALTERATION IN A GLIOBLASTOMA CONTEXT

In the last few years, a growing concern about gut-brain axis has disclosed the relevance of gut-derived metabolites in the intercellular cross-talk occurring in brain parenchyma, both in physiological and pathological contexts. Recently, it has been proved in a murine model of intestinal dysbiosis that alterations in the gut microbiota can increase glycine concentration in the brain parenchyma, and it is now well established that glioblastoma (GBM) metabolism reprogramming relies on glycine availability to support tumor proliferation and vascularization.
Upon oral administration of non-absorbable antibiotics (ABX) in a SCID mouse model of human GBM, we unravel the correlation between the altered composition of gut microbiota and GBM progression. We describe (i) the increment of tumor volume in ABX-treated mice; (ii) the trans-differentiation of GBM cells into endothelial precursor cells, with an increased deposition of extracellular matrix protein laminin surrounding the newly formed vessel-like structures; (iii) the in vitro generation of tumor microtubes in human GBM cell line U87 upon glycine administration; (iv) the glycine-dependent modulation of stemness-related gene expression and endothelial progenitor marker CD34 mRNA, both in U87 and patient-derived GBM cells. In this study, we report that in a SCID mouse model of human GBM gut microbial alteration is responsible for shaping brain microenvironment, and that glycine metabolism contributes to cellular and molecular processes that orchestrate tumor growth and progression.