Oral Supplements of Combined Lactobacillus plantarum and Asparagus officinalis Modulate Gut Microbiota and Alleviate High-Fat Diet-Induced Cognitive Deficits and Neurodegeneration in Rats

High-fat diet (HFD) consumption disrupts the gut microbiome, instigating metabolic disturbance, brain pathology, and cognitive decline via the gut-brain axis. Probiotic and prebiotic supplementation have been found to improve gut microbiome health, suggesting they could be effective in managing neurodegenerative disorders. This study explored the potential benefits of the probiotic strain Lactobacillus plantarum 20174 (L. plantarum), prebiotic Asparagus officinalis (A. officinalis) extract, or their synbiotic combination against HFD-induced cognitive dysfunction and neurodegeneration in rats. Male Sprague-Dawley rats were fed either a normal diet or an HFD for 24 weeks. Starting from week 13, rats on either diet were divided into vehicle-, prebiotic-, probiotic-, and synbiotic-treated subgroups. Rats received their assigned intervention for 12 more weeks. Prebiotic, probiotic, or synbiotic treatment reverted HFD-instigated alterations in hippocampal amyloid beta, p-tau, α-synuclein, and BDNF levels, leading to restored cognitive function. The tested therapies also improved the HFD-disrupted lipid profile. Interestingly, probiotic and synbiotic therapies attenuated oxidative stress and inflammation, reinstated neurotransmitter balance, and mitigated the energy deficit in HFD-fed rats. Furthermore, L. plantarum and Asparagus administration modulated gut microbiota composition by raising Lactobacillus species and reducing Coliform and Staphylococci bacteria as well as fungi populations. These findings suggest that the oral consumption of A. officinalis prebiotics and/or L. plantarum probiotics alleviates HFD-induced cognitive deficit and neurodegeneration through modulation of the gut-brain axis with superior restorative effects being achieved by synbiotic treatment.