Lab4 protects against neurodegenerative decline in Alzheimer's Disease (AD)-prone 3xTG-AD mice

The gut-brain-axis continues to be one of the most studied areas of neurodegenerative health. While the presentation, severity and aetiology of Alzheimer's Disease (AD) can often be predicted by host genetic risk factors, diet, nutrition and microbiome composition are now recognised as major contributors towards this complex disease. Recent studies indicate that diets with poor nutritional value such as the high-fat “western-style” diet (HFD) are major drivers of AD and can elicit these effects via the microbiome and through heightened inflammation. Probiotics are live bacteria that have been shown to play a role in inflammatory dampening, weight gain and cholesterol management and microbiome modulation and numerous studies have demonstrated benefits of probiotic supplementation on hallmarks of AD onset and development. In this study, we supplemented 3xTG-AD mice fed a HFD with Lab4 probiotics to determine (i) the response of 3xTG-AD mice to HFD with regards to cognitive decline, and (ii) the impact of probiotics on the changes induced by HFD. The HFD induced weight gain in mice, which was ameliorated with Lab4 supplementation. Plasma triglycerides and vLDL/LDL were significantly elevated with the HFD, but not with Lab4 supplementation. HFD-induced cognitive decline was rescued by Lab4 supplementation, as was hippocampal spine degeneration. Finally, these data were supported by reductions in brain tissue mRNA expression of caspase-1 and farnesoid X receptor (FXR). The data suggest that the Lab4 consortia of probiotics can produce beneficial effects in AD-prone mice in a metabolically challenged setting.