Comparative Effects of Co-administration of Lactobacillus casei and Bifidobacterium breve vs. Monotherapy on Hippocampal Neurodegeneration in a D-Galactose-Induced Aging Model.

It has been shown that gut dysbiosis, a hallmark of aging, participates in age-related neurodegenerative conditions. Consumption of probiotics has favorable effects not only on gut hemostasis but also on the brain via the microbiota-gut-brain axis. Ongoing research aims to identify the most suitable probiotic or combination of probiotics tailored to each specific condition. Hence, the present study tested the effects of combination therapy of Lactobacillus casei (L. casei) and Bifidobacterium breve (B. breve) on the memory and some potential molecular mechanisms of a mouse aging model. Male Balb/C mice were subcutaneously injected with D-galactose to induce aging and orally supplemented with L. casei and B. breve for 8 weeks. The results showed that treatment with L. casei, B. breve, or their co-administration during the aging process improves the impairment of alternation and locomotion behavior in a Y-maze test. Gene expression analysis revealed that consumption of L. casei and B. breve upregulates α-KL, Sirt1, HO-1, and Nrf2 and suppresses IL-1β and IL-18 gene expression in the right hippocampus. Probiotics treatment also reduced the oxidative stress biomarker malondialdehyde (MDA), increased superoxide dismutase (SOD), and mitigated histopathological changes and neurodegeneration in the left hippocampus. Moreover, the level of fluorescent intensity of BDNF was higher in probiotics-receiving groups. Considerably, our study reveals that L. casei shows better performance compared to B. breve, and the combination therapy appears to exhibit a synergistic effect. Together, these findings suggest that a combination of L. casei and B. breve may have better therapeutic potential than monotherapy for controlling oxidative stress and neurodegeneration in aging.