Zonulin as Gatekeeper in Gut-Brain Axis: Dysregulation in Glioblastoma

Novel biomarkers and therapeutic strategies for glioblastoma, the most common malignant brain tumor with an extremely unfavorable prognosis, are urgently needed. Recent studies revealed a significant upregulation of the protein zonulin in glioblastoma, which correlates with patient survival. Origina...

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Bibliographic Details
Published in:Biomedicines 2024-07, Vol.12 (8), p.1649
Main Authors: Hagemeyer, Hannah, Hellwinkel, Olaf J C, Plata-Bello, Julio
Format: Article
Language:English
Subjects:
Antitumor activity
Bacteria
Blood vessels
Blood-brain barrier
Brain cancer
Brain research
Brain tumors
Carcinogenesis
Celiac disease
Chronic fatigue syndrome
Cytokines
Development and progression
Digestive system
Gastrointestinal tract
Glioblastoma
Glioblastoma multiforme
Glioma
Growth factors
Haptoglobin
Health aspects
Hypotheses
Immune response
Immune system
Intestinal microflora
Kinases
Microbiomes
Microbiota
Microbiota (Symbiotic organisms)
Microenvironments
Microorganisms
Pathogens
Peptides
Permeability
pre-haptoglobin
Proteins
Regulation
Review
Schizophrenia
Tight junctions
zonulin
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Summary:Novel biomarkers and therapeutic strategies for glioblastoma, the most common malignant brain tumor with an extremely unfavorable prognosis, are urgently needed. Recent studies revealed a significant upregulation of the protein zonulin in glioblastoma, which correlates with patient survival. Originally identified as pre-haptoglobin-2, zonulin modulates both the intestinal barrier and the blood-brain barrier by disassembling tight junctions. An association of zonulin with various neuroinflammatory diseases has been observed. It can be suggested that zonulin links a putative impairment of the gut-brain barrier with glioblastoma carcinogenesis, leading to an interaction of the gut microbiome, the immune system, and glioblastoma. We therefore propose three interconnected hypotheses: (I) elevated levels of zonulin in glioblastoma contribute to its aggressiveness; (II) upregulated (serum-) zonulin increases the permeability of the microbiota-gut-brain barrier; and (III) this creates a carcinogenic and immunosuppressive microenvironment preventing the host from an effective antitumor response. The role of zonulin in glioblastoma highlights a promising field of research that could yield diagnostic and therapeutic options for glioblastoma patients and other diseases with a disturbed microbiota-gut-brain barrier.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12081649