Probiotics BB-12 and Bifico Attenuate Radiation-Induced Brain Injury and Cognitive Dysfunction via Modulation of the Mi-crobiota-Gut-Brain Axis

Whole brain irradiation (WBI) is an essential treatment for brain tumors and metastases, but often leads to radiation-induced brain injury (RIBI), and cognitive dysfunction, significantly impairing patients' quality of life. Emerging evidence highlights the role of gut microbiota dysbiosis in neurological disorders via the microbiota-gut-brain axis (MGBA). This study investigated the neuroprotective effects of probiotics Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Bifico on WBI-induced cogni-tive impairment in mice. After 4 weeks of BB-12 and Bifico inter-vention, the cognitive performance of WBI mice in Y-maze and Morris water maze (MWM) tests improved significantly. The interventions also mitigated impairments in hippocampal neurogenesis, reduced the overactivation of microglia and astrocytes, and alleviated neuroinflammation. 16S rRNA sequencing revealed that WBI-induced gut microbiota dysbiosis, characterized by reduced alpha diversity and increased Hel-icobacter abundance, was reversed by probiotic treatment. Additionally, BB-12 and Bifico restored intestinal barrier integrity, as indicated by upregulated tight junction proteins, and reduced colonic and systemic inflammation. This study suggests that probiotics BB-12 and Bifico promote recovery from RIBI and cognitive dysfunction by modulating the MGBA, providing new insights into potential strategies for intervening in RIBI and cognitive dysfunction.