Weissella confusa Attenuates Cognitive Deficits in Alzheimer's Disease by Reducing Oxidative Stress Via the SIRT1/PGC-1α Signaling Pathway.

Emerging evidence suggests that probiotics may have a significant impact on the regulation of mitochondrial oxidative stress in Alzheimer's disease (AD). However, the research focusing on the specific bacteria responsible for mitochondrial oxidative stress of AD remains limited. This study explores the impact and underlying mechanisms of probiotic W. confusa WMU005 on mitochondrial oxidative stress in AD. The probiotic W. confusa WMU005 was isolated from the healthy people. APP/PS1 mice were administered live W. confusa WMU005 for 4 weeks and then subjected to cognitive test. Aβ deposition, Tau phosphorylation, neuronal apoptosis, oxidative stress, and mitochondrial damage of brain were measured. Additionally, APP/SWE cells treated with W. confusa WMU005 fermentation broth showed altered levels of silent information regulator 1 (SIRT1) and proliferator-activated receptor γ coactivator 1α (PGC-1α). Meanwhile, we confirmed that W. confusa WMU005 could regulate SIRT1 pathway in APP/PS1 mice. Our results revealed that W. confusa WMU005 improved cognitive function, reduced Aβ and Tau pathology. Furthermore, W. confusa WMU005 treatment exerted antioxidative effects by activating the SIRT1 pathway. We further demonstrated that W. confusa WMU005 mitigated the mitochondrial oxidative stress via activating SIRT1 pathway in vitro. Meanwhile, we revealed that W. confusa WMU005 effectively inhibited the mitochondrial oxidative stress in the APP/PS1 mice by regulating SIRT1 pathway. These findings suggest that W. confusa WMU005 exerts protective effects on AD through the involvement of the SIRT1 signaling pathway, which opened avenues for novel therapeutic strategies towards treating AD.