# Bidirectional interactions along the microbiota–gut–brain axis in radiation-induced brain injury: mechanisms and therapeutic insights

**Authors:** Yayi Yuan, Nan Wang, Kang Ning, Xuhong Dang

PMC · DOI: 10.3389/fonc.2026.1774021 · Frontiers in Oncology · 2026-02-05

## TL;DR

This paper reviews how gut-brain communication influences brain injury from radiation therapy and suggests new ways to treat it.

## Contribution

It provides a novel framework for understanding radiation-induced brain injury through the microbiota–gut–brain axis.

## Key findings

- The microbiota–gut–brain axis plays a role in radiation-induced brain injury mechanisms.
- Bidirectional interactions involve neuroimmune responses, inflammation, DNA damage, and oxidative stress.
- Targeting the microbiota–gut–brain axis could lead to new therapeutic strategies for RBI.

## Abstract

Radiation therapy is widely used for the treatment of brain tumors and metastases from extracranial malignancies; however, it may also cause damage to normal brain tissue, potentially resulting in radiation-induced brain injury (RBI). Emerging evidence highlights the microbiota–gut–brain axis (MGBA) as a critical mediator of bidirectional communication between the gut microbiota and the brain, playing an important role in central nervous system (CNS) homeostasis and pathology. This review aims to summarize current evidence regarding the potential involvement of the MGBA in the pathogenic mechanisms of RBI, with particular emphasis on bidirectional interactions along this axis. We focus on underlying mechanisms, including neuroimmune and inflammatory responses, signal transduction, DNA damage, and oxidative stress. By integrating these perspectives, this review seeks to provide a novel conceptual framework for understanding RBI and to identify potential directions for future MGBA-targeted interventions.

## Full-text entities

- **Genes:** P2ry13 (purinergic receptor P2Y, G-protein coupled 13) [NCBI Gene 74191] {aka 2010001L06Rik, GPCR1, GPR94, Gpr86, P2Y13, P2yr13}, Tgfa (transforming growth factor alpha) [NCBI Gene 21802] {aka wa-1, wa1}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, Vegfb (vascular endothelial growth factor B) [NCBI Gene 22340] {aka VEGF-B, Vrf}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Atr (ataxia telangiectasia and Rad3 related) [NCBI Gene 245000], Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, 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}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Hdac1 (histone deacetylase 1) [NCBI Gene 433759] {aka HD1, Hdac1-ps, MommeD5, RPD3}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Cldn5 (claudin 5) [NCBI Gene 12741] {aka MBEC1, Tmvcf}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Lamp1 (lysosomal-associated membrane protein 1) [NCBI Gene 16783] {aka CD107a, LGP-120, LGP-A, Lamp-1, P2B, Perk}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Ahr (aryl-hydrocarbon receptor) [NCBI Gene 11622] {aka Ah, Ahh, Ahre, In, bHLHe76}, Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, S1pr2 (sphingosine-1-phosphate receptor 2) [NCBI Gene 14739] {aka 1100001A16Rik, Edg5, Gpcr13, H218, LPb2, S1P2}, P2ry12 (purinergic receptor P2Y, G-protein coupled 12) [NCBI Gene 70839] {aka 2900079B22Rik, 4921504D23Rik, P2Y12}, Tnfsf10 (tumor necrosis factor (ligand) superfamily, member 10) [NCBI Gene 22035] {aka A330042I21Rik, APO-2L, Ly81, TL2, Tnlg6a, Trail}, Gpbar1 (G protein-coupled bile acid receptor 1) [NCBI Gene 227289] {aka BG37, GPCR, GPR131, M-BAR, TGR5}, Apoe (apolipoprotein E) [NCBI Gene 11816] {aka Apo-E}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}
- **Diseases:** neuroinflammation (MESH:D000090862), head and neck tumors (MESH:D006258), BBB damage (MESH:C536830), extracranial malignancies (MESH:D009369), Gut dysbiosis (MESH:D064806), neurotoxic (MESH:D020258), mitochondrial dysfunction (MESH:D028361), Inflammatory (MESH:D007249), neurodegenerative (MESH:D019636), neural injury (MESH:D014947), neurological deficits (MESH:D009461), microbial (MESH:D015163), radiation proctitis (MESH:D011349), cerebral edema (MESH:D001929), toxicity (MESH:D064420), vascular injury (MESH:D057772), brain lesions (MESH:D001927), -induced brain injury (MESH:D001930), demyelination (MESH:D003711), metastases (MESH:D009362), memory deficits (MESH:D008569), RBI (MESH:D011832), brain tumors (MESH:D001932), cognitive decline (MESH:D003072), intestinal damage (MESH:D007410), cell injury (MESH:D002280), dysfunction (MESH:D006331), neuronal injury (MESH:D009410)
- **Chemicals:** kynurenic acid (MESH:D007736), glucosides (MESH:D005960), IPA (MESH:C000723775), deoxycholic acid (MESH:D003840), cAMP (MESH:D000242), quinolinic acid (MESH:D017378), prostaglandin F2alpha (MESH:D015237), Kynurenine (MESH:D007737), N6-carboxymethyllysine (MESH:C048496), taurocholic acid (MESH:D013656), Acetylcholine (MESH:D000109), 137Cs (MESH:C000614989), UroA (MESH:C026423), Propionate (MESH:D011422), phenylacetylglutamine (MESH:C003089), Butyrate (MESH:D002087), Bile Acids (MESH:D001647), BioRender (-), calcium (MESH:D002118), ROS (MESH:D017382), SCFA (MESH:D005232), Indole (MESH:C030374), 5-HT (MESH:D012701), ellagic acid (MESH:D004610), Tryptophan (MESH:D014364), LPS (MESH:D008070)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Escherichia coli (E. coli, species) [taxon 562], Citrobacter (genus) [taxon 544], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Limosilactobacillus reuteri (species) [taxon 1598], Enterobacteriaceae (enterobacteria, family) [taxon 543]

## Full text

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## Figures

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## References

92 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916379/full.md

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Source: https://tomesphere.com/paper/PMC12916379