Abstract: This study aimed to investigate the impact of three postbiotics at different doses on cognitive function in a rat model of Alzheimer’s disease (AD) induced by D-galactose combined with AlCl3. Specific pathogen-free (SPF) Wistar rats were randomly divided into nine groups: control (Ctrl), AD model, positive drug (donepezil hydrochloride), low-dose (108 CFU/kg) and high-dose (109 CFU/kg) Bifidobacterium animalis spp. lactis IOBL07, Lactiplantibacillus plantarum IOB602 and L. paracasei IOB413. The Ctrl group was intraperitoneally and orally administered with normal saline, while all other experimental groups were subjected to intraperitoneal injection of D-galactose and oral gavage of AlCl3. The model induction period lasted for 13 consecutive weeks. At 1 h following the last injection and oral gavage, the intervention groups were orally administered with donepezil hydrochloride or postbiotics, whereas the Ctrl and AD groups were given an equivalent volume of normal saline. The Morris water maze was used to assess the learning and memory capacities of the rats in each group. Additionally, the content and immunofluorescence intensity of amyloid β-protein (Aβ) in hippocampal tissues were determined. Histopathological changes in the small intestine were examined along with changes in the intestinal microbiota. The levels of lipopolysaccharide (LPS) in feces, serum, and hippocampal tissues were determined as well as the relative mRNA transcription levels of toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and myeloid differentiation factor 88 (MyD88) in brain tissues. The results showed that all three postbiotics could significantly improve the learning and memory capacities of AD rats, significantly reduce the content of Aβ in hippocampal tissues, and decrease the LPS levels in feces, serum, and hippocampal tissues and the relative mRNA transcription levels of TLR4, NLRP3 and MyD88 in brain tissues. Intervention with the postbiotics regulated the structure and composition of the intestinal microbiota. In the postbiotic intervention groups, the relative abundance of the predominant intestinal bacteria, Firmicutes, and the beneficial species, Ruminococcaceae increased, the relative abundance of the potential harmful intestinal bacteria, Muribaculaceae, decreased compared with the AD model group. Thus, the postbiotics IOBL07, IOB602, and IOB413 have significant efficacy in ameliorating memory and cognitive deficits in AD rats, the most pronounced effect being observed with high-dose IOB602. The underlying mechanisms might be associated with regulating the structure and composition of the gut microbiota and down-regulating the relative mRNA transcription levels of TLR4, NLRP3 and MyD88 in brain tissues.

Key words: Alzheimer’s disease, postbiotics, cognitive impairment, gut microbiota, inflammatory factors