Three hypotheses can be proposed explaining the interplay of zonulin and glioblastoma: elevated zonulin levels (I) contribute to glioblastoma aggressiveness, (II) they mechanistically increase the permeability of the microbiota–gut–brain axis in glioblastoma, and (III) they contribute significantly to a tumorigenic microenvironment and the impairment of the host to eliminate tumor cells. This evidence concerns the gene HP and neoplasm.