# From the gut to the brain: The involvement of the gut microbiota in the development and progression of glioblastoma

**Authors:** Daniela Toumazi, Christiana Charalambous, Constantina Constantinou, Nicoletta Nicolaou

PMC · DOI: 10.1093/noajnl/vdaf267 · 2025-12-22

## TL;DR

This paper reviews how gut microbiota influences glioblastoma development and treatment through the gut-brain axis, suggesting new therapeutic approaches.

## Contribution

The paper provides a comprehensive review of the gut microbiota's role in glioblastoma and potential microbiota-targeted therapies.

## Key findings

- Gut microbiota can modulate immune responses and inflammatory pathways affecting glioblastoma progression.
- Fecal microbiota transplantation and bacterial toxins show promise in treating glioblastoma.
- Probiotics and antibiotics may influence glioblastoma prognosis, but more research is needed.

## Abstract

Glioblastoma (GB) is the most malignant tumor in the adult central nervous system (CNS), presenting substantial treatment challenges due to its infiltrative nature, heterogeneity and immunosuppressive environment it creates. Current therapeutic efforts are focused on enhancing our understanding of GB and developing effective therapies. An emerging area of interest is the bidirectional gut–brain axis, which mediates communication between gut microbiota and CNS. The gut–brain axis allows the microbiota to modulate the immune system and inflammatory pathways through microbial metabolites, such as short-chain fatty acids (SCFAs) and tryptophan derivatives, promoting or suppressing GB progression. Understanding these interactions can lead to microbiota-targeted therapies for GB patients. Novel therapies, such as fecal microbiota transplantation to enhance immunotherapy response and using bacterial toxins to cross the blood–brain barrier, show promise in improving treatment-resistant GB treatment. Additionally, the role of probiotics and antibiotics on GB prognosis is being investigated. While more research is needed to understand the gut microbiota’s role in GB, recent findings suggest promising directions for future therapies. This review examines the interplay between key immune system components and the microbiota in GB development and explores how this understanding could facilitate the development of novel therapeutic interventions.

## Linked entities

- **Diseases:** glioblastoma (MONDO:0018177)

## Full-text entities

- **Genes:** Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, Idh1 (isocitrate dehydrogenase 1 (NADP+), soluble) [NCBI Gene 15926] {aka E030024J03Rik, Id-1, Idh-1, Idpc}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, Ffar2 (free fatty acid receptor 2) [NCBI Gene 233079] {aka GPCR43, Gpr43}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 953] {aka ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, KLF13 (KLF transcription factor 13) [NCBI Gene 51621] {aka BTEB3, FKLF2, NSLP1, RFLAT-1, RFLAT1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, DRD2 (dopamine receptor D2) [NCBI Gene 1813] {aka D2DR, D2R}, Cd27 (CD27 antigen) [NCBI Gene 21940] {aka S152, Tnfrsf7, Tp55}
- **Diseases:** hypoxic (MESH:D002534), colorectal, breast, and gastric cancers (MESH:D013274), GB Carcinogenesis (MESH:D063646), neurotoxicity (MESH:D020258), psychiatric conditions (MESH:D001523), Tumor (MESH:D009369), Dysbiosis (MESH:D064806), neuroinflammation (MESH:D000090862), CNS disorders (MESH:D002493), inflammation (MESH:D007249), neurodegenerative disorders (MESH:D019636), melanoma (MESH:D008545), Glioma (MESH:D005910), necrotic (MESH:D009336), GB (MESH:D005909), brain tumor (MESH:D001932), aggressiveness (MESH:D010554), colitis (MESH:D003092), CNS tumors (MESH:D016543), cytotoxic (MESH:D064420), GAM (MESH:D055501), carcinogens (MESH:D011230), brain disorders (MESH:D001927), colorectal cancer (MESH:D015179)
- **Chemicals:** Noradrenaline (MESH:D009638), GABA (MESH:D005680), Glutamate (MESH:D018698), kynurenine (MESH:D007737), gamma-PGA (MESH:C511775), tyrosine (MESH:D014443), salinomycin (MESH:C010327), indoles (MESH:D007211), Acetylcholine (MESH:D000109), propionic acid (MESH:C029658), cortisol (MESH:D006854), adenosine (MESH:D000241), sucralose (MESH:C026285), Inosine (MESH:D007288), deoxycholic acid (MESH:D003840), Dopamine (MESH:D004298), acetate (MESH:D000085), tryptophan (MESH:D014364), spermidine (MESH:D013095), Serotonin (MESH:D012701), SCFA (MESH:D005232), Polyamines (MESH:D011073), LPS (MESH:D008070), Butyrate (MESH:D002087), TMZ (MESH:D000077204), lithocholic acid (MESH:D008095), propionate (MESH:D011422), putrescine (MESH:D011700), 5-hydroxyindoleacetuc acid (-), Bile acids (MESH:D001647), Clofoctol (MESH:C018874), 5-HIAA (MESH:D006897)
- **Species:** Enterococcus (genus) [taxon 1350], Streptococcus pyogenes (species) [taxon 1314], Mus musculus (house mouse, species) [taxon 10090], Mediterraneibacter gnavus (species) [taxon 33038], Lactobacillus (genus) [taxon 1578], Faecalibacterium (genus) [taxon 216851], Salmonella (genus) [taxon 590], Escherichia coli (E. coli, species) [taxon 562], Anaerostipes (genus) [taxon 207244], gut metagenome (species) [taxon 749906], Bacteroidia (class) [taxon 200643], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Bacteroides cellulosilyticus (species) [taxon 246787], Bacteroides fragilis (species) [taxon 817], Bacteroides intestinalis (species) [taxon 329854], Fusobacterium (genus) [taxon 848], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Bifidobacterium (genus) [taxon 1678], Microbiota (genus) [taxon 13613], Akkermansia muciniphila (species) [taxon 239935], Lachnospira (genus) [taxon 28050], Fusobacteriia (class) [taxon 203490], [Eubacterium] brachy (species) [taxon 35517], Burkholderiales (order) [taxon 80840]
- **Cell lines:** T-Helper — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_3174), GL261 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_Y003), HuM1-5 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_L351)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12924637/full.md

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Source: https://tomesphere.com/paper/PMC12924637