The gut microbiota-brain axis in Alzheimer’s disease model mice

Nov 16, 2025Physiology & behavior

How Gut Bacteria Affect Alzheimer's Disease in Mice

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Abstract

APP/PS1 mice exhibited a significant increase in β-amyloid deposition and hyperphosphorylated tau proteins compared to wild-type mice.

Increased activation of microglia was observed in the hippocampus and cortex of APP/PS1 mice.
Distinct bacterial community changes were identified in APP/PS1 mice through 16S rRNA sequencing.
In APP/PS1 mice, there was greater abundance of specific bacteria such as Muribaculaceae and Ligilactobacillus.
Conversely, there was a decrease in the abundance of Lachnospiraceae_NK4A136_group and Clostridia_UCG-014 in APP/PS1 mice.
These findings suggest a possible association between gut microbiota alterations and Alzheimer's disease under pathogenetic stress.

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The gut microbiota plays a pivotal role in the pathogeneses of Alzheimer's disease (AD), influencing neuroinflammation and disease progression. Understanding the role of the gut microbiota in this process is critical for uncovering novel therapeutic avenues and deepening insights into AD pathogenesis. Nevertheless, the specific gut microbiota alterations under pathogenetic stress in AD remain unclear. In this study, immunofluorescence was performed to detect β-amyloid (Aβ) deposition, hyperphosphorylated tau proteins (P-tau), and the activation of microglia in the brains of APPswe/PSEN1dE9 transgenic (APP/PS1) mice and C57BL/6 J wild-type (WT) mice. Congo red staining and thioflavin-S staining were used to detect Aβ plaques accumulation in the hippocampus and cortex. 16S rRNA sequencing was used to elucidated the bacteria changes between the APP/PS1 and WT mice. The results of immunofluorescence and pathological stainings exhibited that the APP/PS1 mice showed significant increase of Aβ deposition and P-tau, and greater activation of microglia in the hippocampus and cortex, compared with WT mice. 16S rRNA sequencing identified increased abundance of Muribaculaceae, Ligilactobacillus, Dubosiella, Limosilactobacillus, Alistipes, Lactobacillus, and Enterorhabdus, and decreased abundance of Lachnospiraceae_NK4A136_group, Clostridia_UCG-014, and Lachnospiraceae _UCG-006 in APP/PS1 mice, revealing distinct hub bacteria with AD under pathogenetic pressure.

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The gut microbiota-brain axis in Alzheimer’s disease model mice

Abstract

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