Bacterial Supplementation Reverses Gut‒Brain Axis Disruption in Pelvic Irradiation by Restoring Bacteria-Derived Neuroactive Metabolites

Pelvic radiotherapy induces gut dysbiosis that propagates neurotoxicity via the microbiota-gut-brain axis. In Sprague-Dawley rats exposed to 6 Gy pelvic irradiation, prophylactic/therapeutic multi-strain probiotics restored depleted beneficial taxa (Lactobacillaceae, Butyricicoccaceae, Ruminococcaceae) and reduced opportunistic pathogens. Untargeted LC-MS brain metabolomics (3,535 metabolites; 84 microbial-derived) revealed radiation-altered compounds from Proteobacteria, Firmicutes, Ascomycota, Actinobacteria affecting xenobiotic degradation, oxidative stress, lipid signaling, and neurotransmitter pathways. Prophylactic-therapeutic supplementation recovered allantoin, PA(18:0/15:0), and reactivated neuroprotective cascades, linking microbiome restoration to brain metabolome normalization.

Keywords: gut dysbiosis, pelvic radiation, microbiota-gut-brain axis, probiotics, LC-MS metabolomics, neuroprotection

Organism: Rattus norvegicus (Sprague-Dawley rats, male, 3-4 months)

Experimental Factors: Treatment Variant (Control, Radiation, Bacterial supplements, Combination)

Technology Type: 16S rRNA sequencing; Untargeted LC-MS metabolomics

Study Design: Multi-omics analysis of radiation-induced brain metabolome changes and probiotic mitigation.