The preventive effects of probiotic Akkermansia muciniphila on D-galactose/AlCl3 mediated Alzheimer's disease-like rats.

Aims: We induced the AD-like rat models injected by AlCl and D-galactose, to explore the effects of an oral treatment of A. muciniphila on AD-like rats with periodontitis and its possible mechanism.

Main Methods: We used Morris water maze test and micro-CT to assess the cognitive impairment and bone loss; Aβ1-42 deposition was tested by IHC; Serum LPS level and TG, HDL-C and AST/ALT levels were detected by LAL Test and biochemical tests; The gut microbiota was analyzed by 16S rRNA gene sequence.

Key Findings: We found that A. muciniphila could alleviate AD-like rats' cognitive impairment and mitigate ligature-induced periodontitis. Furthermore, A. muciniphila reduced Aβ1-42 deposition in the cortex and regions of the rats' brain, and altered TG, HDL-C and AST/ALT levels but had little ability to change circulating LPS level and cross the blood-brain barrier. Notably, A. muciniphila treatment could improve the abundance of some short chain fatty acid (SCFA)-producing or neurotransmitter-producing gut microbiome such as Blautia, Staphylococcus and Lactococcus, while the abundance of pathogenic Aerococcus and Streptococcus, which were associated inflammation, were decreased.

Significance: Our findings suggested that A. muciniphila has a remissive effect on AD-like pathologies, potentially by regulating gut-brain axis through altering composition and function of gut microbial community or moderating peripheral circulation metabolism.