Amelioration of cognitive impairment using epigallocatechin-3-gallate in ovariectomized mice fed a high-fat diet involves remodeling with Prevotella and Bifidobacteriales

Abstract

Background: Estrogen deficiency and a high-fat diet (HFD) are both risk factors for Alzheimer’s disease (AD). HFD can accelerate cognitive impairment in estrogen-deficient patients, but there is currently no effective treatment. Epigallocatechin-3-galate (EGCG) is widely studied for its anti-inflammatory, anti-cancer, and anti-neurodegeneration effects. Nevertheless, whether EGCG can ameliorate cognitive impairment in HFD-fed estrogen-deficient mice has not been studied.Methods and Results: Ovariectomized (OVX) mice fed an HFD (HFOVX) for 8 weeks experienced impaired object recognition and spatial memory, but this damage was significantly attenuated by the administration of EGCG at a dose of 45 mg/kg. Through 16S rRNA gene sequencing, we found that HFOVX changed the diversity and structure of the gut microbiota in mice, which could be restored with EGCG. Further analysis showed that HFOVX exposure not only resulted in a decrease of Alloprevotella in Bacteroidetes, Lactobacillaceae in Firmicutes, and Prevotella in Bacteroidetes but also in an increase of Bifidobacteriales in Actinobacteria. EGCG effectively reversed the decrease of Prevotella and inhibited the increase of Bifidobacteriales but had no effect on the decrease of Alloprevotella or Lactobacillaceae or on the increase of Enterorhabdus in HFOVX mice. Additionally, using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we found that EGCG significantly reversed the five functional gut microbiota genes elevated by HFOVX, including iron complex transport system substrate-binding protein, iron complex transport system permease protein, 3-oxoacyl- [acyl-carrier protein] reductase, transketolase, and 8-oxo-dGTP diphosphatase.Conclusions: We concluded that EGCG improved cognitive impairment in mice with estrogen deficiency exacerbated by an HFD involved a rebuilding of the disrupted gut microbiota composition.

Bioactive nutraceuticals oligo-lactic acid and fermented soy extract alleviate cognitive decline in mice in part via anti-neuroinflammation and modulation of gut microbiota

“…Mice with depression also had increased abundance of Actinobacteria ( 30 ). Ovariectomized (OVX) mice fed a high-fat diet experienced impaired object recognition and spatial memory associated with increased Bifidobacteriales ; administration of epigallocatechin gallate (EGCG) significantly improved cognition and memory and inhibited the increase of Bifidobacteriales ( 31 ). The results in our current study showed that IMB supplementation significantly improved cognition associated with significant reduction of Actinobacteria abundance.…”

Development of dietary small molecules as multi-targeting treatment strategies for Alzheimer's disease

“…In mice with estrogen deficiency and HFD-induced AD, EGCG administration (45 mg/kg bw) for 2 months improved object recognition and spatial memory, restored the diversity and structure of the gut microbiome in HFOVX mice, with increased Prevotella and inhibition of Bifidobacteriales but no effect on the decreases in Alloprevotella and Lactobacillaceae or on the increase in Enterorhabdus ( Fig. 6 ) [ 226 ]. Soto-Mercado et al [ 227 ] subsequently showed that EGCG treatment significantly inhibited the aggregation of (i)sAPPβf, blocked p-tau, increased ΔΨm, decreased oxidation of DJ-1 at residue Cys106-SH, and inhibited the activation of transcription factor c-JUN and P53, PUMA, and caspase-3 in mutant cholinergic-like neurons (ChLNs) compared to wild type.…”