Title: Cadmium exposure modulates the gut-liver axis in an Alzheimer's disease mouse model.

Authors: Zhang, Angela; Matsushita, Megumi; Zhang, Liang; Wang, Hao; Shi, Xiaojian; Gu, Haiwei; Xia, Zhengui; Cui, Julia Yue

Published In Commun Biol, (2021 Dec 15)

Abstract: The human Apolipoprotein E4 (ApoE4) variant is the strongest known genetic risk factor for Alzheimer's disease (AD). Cadmium (Cd) has been shown to impair learning and memory at a greater extent in humanized ApoE4 knock-in (ApoE4-KI) mice as compared to ApoE3 (common allele)-KI mice. Here, we determined how cadmium interacts with ApoE4 gene variants to modify the gut-liver axis. Large intestinal content bacterial 16S rDNA sequencing, serum lipid metabolomics, and hepatic transcriptomics were analyzed in ApoE3- and ApoE4-KI mice orally exposed to vehicle, a low dose, or a high dose of Cd in drinking water. ApoE4-KI males had the most prominent changes in their gut microbiota, as well as a predicted down-regulation of many essential microbial pathways involved in nutrient and energy homeostasis. In the host liver, cadmium-exposed ApoE4-KI males had the most differentially regulated pathways; specifically, there was enrichment in several pathways involved in platelet activation and drug metabolism. In conclusion, Cd exposure profoundly modified the gut-liver axis in the most susceptible mouse strain to neurological damage namely the ApoE4-KI males, evidenced by an increase in microbial AD biomarkers, reduction in energy supply-related pathways in gut and blood, and an increase in hepatic pathways involved in inflammation and xenobiotic biotransformation.

PubMed ID: 34912029

MeSH Terms: Alzheimer Disease/metabolism*; Alzheimer Disease/physiopathology; Animals; Cadmium/metabolism*; Disease Models, Animal; Female; Intestine, Large/metabolism; Liver/metabolism; Male; Mice; Mice, Transgenic; Mumps Vaccine