AUTHOR=Hu Ke , Liao Xing-Xing , Wu Xiao-Yun , Wang Rui , Hu Zi-Wei , Liu Si-Yuan , He Wen-Fen , Zhou Jun-Jie 

TITLE=Effects of the Lipid Metabolites and the Gut Microbiota in ApoE−/− Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.786492

DOI=10.3389/fmolb.2022.786492

ISSN=2296-889X

ABSTRACT=To investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus
regions and the characteristics of the gut microbiota in ApoE-/- mice with atherosclerosis
co-depression. ApoE-/- mice (HFB group, n=14,♂) fed a high-fat diet for 16 weeks with
binding stimulation were used as an animal model for atherosclerosis co-depression.
Compared with NC group mice, HFB group mice showed depression-like behaviors and
atherosclerosis-related pathological indicators. Non-targeted lipidomics analysis by
LC-MS/MS showed that the different lipid metabolites in the prefrontal cortex and
hippocampus regions of HFB and NC groups were mainly LPC, LPE, LPS, PC, PE, PS,
PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and
the retrograde endocannabinoid signaling pathway, which leads to abnormal white matter and
synaptic dysfunction. Sequencing of 16S rDNA amplicons revealed significant differences in
the structure of the gut microbial community between the two groups. Compared with the NC
group, the abundance of Deferribacteres and Proteobacteria in the HFB group increased,
while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level;
the abundance of Desulfovibrio, Clostridium_IV, Helicobacter, and Pseudoflavonifractor
increased, while the abundance of Akkermansia decreased at the genus level, resulting in
increased gut inflammation and decreased gut permeability, which leads to the release of
inflammatory cytokines. Finally, the correlation analysis results showed that the
above-mentioned differential lipid metabolites had a strong correlation with the differential
gut microbiota.