Amelioration of cognitive and behavioral damage by Bifidobacterium breve 05 via regulation of BDNF/NeuN and LPS/Iba1/aβ expression.

Aging can reduce learning and memory abilities. This study investigated the neuroprotective effects of Bifidobacterium breve 05 (B. breve 05), isolated from human breast milk, in a D-galactose-induced cognitive impairment model in C57BL/6 mice. B. breve 05 markedly improved spatial learning, memory, and behavioural performance. Mechanistically, it balanced gut immune responses by modulating pro- and anti-inflammatory cytokines, suppressing NF-κB activation and CD11c⁺ cells. The strain reshaped gut microbiota by inhibiting Allobaculum and enriching beneficial genera (Alistipes and Kineothrix), elevated serum serotonin, GABA, and dopamine, and restored acetylcholine homeostasis via reduced acetylcholinesterase activity. In the hippocampus, treatment with B. breve 05 enhanced NeuN⁺ neurons and BDNF expression, while reducing LPS, amyloid-β, and Iba-1⁺ microglia activation. Collectively, B. breve 05 confers neuroprotection by modulating the microbiota-gut-brain axis and represents a promising probiotic for mitigating stress-related cognitive and behavioural impairments.