A fiber-plus diet in male 5xFAD mice was linked to microbiome and lipid shifts alongside reduced Alzheimer's-like pathology and better cognitive task performance.
Evidence
This is a five-month mouse diet experiment comparing fiber-free with fiber-plus diets and measuring , fecal lipid metabolites, intestinal permeability, neuropathology, synaptic and neurogenesis markers, and behavior.
Caveat
The findings are limited to a 5xFAD mouse model with a defined fiber mixture, so they do not show that dietary fiber prevents or treats Alzheimer's disease in humans.
Simplified
The gut-brain axis plays a critical role in maintaining neuronal integrity and influencing the progression of Alzheimer's disease (AD). Here, we investigated how commonly consumed dietary fibers modulate , lipid metabolism, and AD pathology in 5xFAD mice. Male mice were fed either fiber-free (FF) or fiber-plus (FP; 1% cellulose, 2% pectin, 2% inulin) diets for five months, followed by integrated analyses of gut microbiota (16 S rRNA sequencing), fecal lipid metabolites (LC-MS/MS), and neuropathological and behavioral outcomes. FP diets markedly altered microbial composition, characterized by increases in Muribaculaceae, Ileibacterium, and Lachnospiraceae NK4A136 group and reductions in Faecalibaculum and Coriobacteriaceae UCG-002. Fecal lipidomics revealed significant shifts in phospholipids and long-chain fatty acids, while short-chain fatty acid levels showed only modest, taxa-specific changes. Functionally, FP-fed AD mice exhibited reduced (Aβ) deposition, lower microglial activation, improved microglial morphology, and a decreased cortical and hippocampal Aβ42/Aβ40 ratio. Moreover, FP diets enhanced hippocampal neurogenesis, preserved synaptic protein expression, and improved cognitive performance in object recognition and Y-maze tasks. FP supplementation also mitigated the increased intestinal permeability observed in AD mice. Together, these findings demonstrate that dietary fiber modulates the microbiome-lipid axis and attenuates AD-related pathology through mechanisms extending beyond SCFA production, supporting dietary interventions as a promising strategy for AD prevention and therapy.
Key numbers
12 of 12 mice
Increase in cognitive performance
In the novel object recognition test, FPAD mice preferred novel objects.
/ ratio significantly decreased
Decrease in / ratio
analysis showed reduced Aβ levels in FPAD mice.
FITC-dextran levels significantly decreased
Reduction in gut permeability
FPAD mice exhibited reduced FITC-dextran concentrations in serum.
Full Text
We can’t show the full text here under this license.
