Hawthorn flavonoid ameliorates cognitive deficit in mice with Alzheimer's disease by increasing the levels of Bifidobacteriales in gut microbiota and docosapentaenoic acid in serum metabolites

Abstract

Hawthorn flavonoid (HF) exhibits potential benefits in Alzheimer’s disease (AD), but its mechanism of action remains elusive. In this study, we identified the main components of HF, demonstrating that the...

Dietary (Poly)phenols and the Gut–Brain Axis in Ageing

“…When the gut homeostasis is compromised, anti-inflammatory molecules such as SCFAs are decreased and an imbalance occurs with levels of pro-inflammatory molecules (e.g., LPS or biofilm amyloid fibres) [97,98] resulting in greater permeability of the intestinal wall, increased mitochondrial ROS production, neuronal peroxisome proliferation, as well as neurotoxin aggregation and, potentially, neurodegeneration. The decline in free radicals in the brain, through the reduction of oxidation by the modulation of the gut microbiome with the consumption of (poly)phenolic compounds, is reflected by the decrease in the level of malondialdehyde (MDA) and ROS, which is concordant with the changes in SCFAs production or the increase in SCFA-producing bacteria in several studies [74,80,82,85,[99][100][101][102][103][104][105][106] (Table 1). This interplay between gut microbiota and brain oxidative stress highlights the potential of the gut microbiome to modulate the brain redox status.…”

“…(Poly)phenol-rich extracts and botanicals, such as blackberry and blueberry anthocyanin-rich extracts [78,79], have been shown to restore gut dysbiosis, increase the production of SCFAs, improve cognitive performance and improve antioxidant activities in the brain. Overall, (poly)phenols improve gut microbiome composition by increasing microbial abundance and diversity and by restoring a gut microbial balance between the Firmicutes/Bacteroidetes ratio [74,[80][81][82].…”

“…This interplay between gut microbiota and brain oxidative stress highlights the potential of the gut microbiome to modulate the brain redox status. Furthermore, there is also a consensus regarding (poly)phenol consumption, the gut microbiome ecosystem and brain integrity, via the maintenance of BBB, improvement of synaptic activity, and the overall reduction of inflammation in the brain [68,77,80,107,108]. In some cases, there is a parallel between the observed increase in SCFA levels, or the increase in SCFA-producing bacteria and a positive regulation of astrocyte and microglial activity in the brain, hence collectively supporting neuronal activity [68,107,108].…”

“…This is notably illustrated by an a posteriori increase in neuroinflammation, which was observed following menopause and the associated fall in oestrogen levels [109,110]. In models of (neuro)inflammatory diseases, e.g., direct administration of amyloid beta Aβ1-42 peptide [111], D-galactose [68,[80][81][82]99,104,105] or by other neurotoxins [111], oxidative stress, inflammation and mitochondrial dysfunction occur, usually in parallel to an abnormal gut ecosystem. This is of major importance as it validates the bidirectionality of the gut-brain axis, with induced neuro-disorders causing deleterious changes at the level of the microbiome.…”

Gut microbiota-host lipid crosstalk in Alzheimer’s disease: implications for disease progression and therapeutics

“…Oral administration of 200 mg/kg hawthorn flavonoid (HF) increased the proportion of Dubosiella and Alloprevotella, reversing gut Table 1 Current research on the gut microbiota-based therapy in improving AD lipid metabolism and pathological features microbiota and metabolic disturbances in AD mice. This led to elevated levels of docosapentaenoic acid (DPA), sphingolipids, and PC, significantly ameliorating cognitive deficits, Aβ accumulation, and abnormal activation of hippocampal astrocytes in AD mice [251]. Curcumin reduced the abundance of Prevotellaceae, Bacteroides, and Escherichia/Shigella in the gut of APP/PS1 mice.…”