Based on heightened zonulin production in glioblastoma, three hypotheses can be proposed, potentially enhancing each other in a vicious cycle: (I) zonulin contributes to tumor aggressiveness; (II) the elevated zonulin levels in glioblastoma and the corresponding blood-stream increase the permeability of the microbiota–gut–brain axis; and (III) higher trafficking of microbiota and immune cells subsequently induces a chronic inflammatory and carcinogenic microenvironment. This evidence concerns the gene HP and glioblastoma.