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. 2023 Dec;15(2):2282790.
doi: 10.1080/19490976.2023.2282790. Epub 2023 Nov 22.

Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice

Xiaohang Qian  1   2   3 , Wangxi Hai  4 , Siyue Chen  3 , Miao Zhang  4 , Xufeng Jiang  4 , Huidong Tang  1   2
Affiliations

Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice

Xiaohang Qian et al. Gut Microbes. 2023 Dec.

Abstract

Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.

Keywords: Alzheimer’s disease; glycerophospholipid metabolism; gut microbiota; multi-omics; neuroinflammation.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Experimental design.
Figure 2.
Figure 2.
Cognitive level and neuropathology in APP/PS1 and WT mice.
Figure 3.
Figure 3.
The difference of gut microbiota between APP/PS1 and WT mice.
Figure 4.
Figure 4.
The difference of metabolites in serum and brain of APP/PS1 and WT mice.
Figure 5.
Figure 5.
Difference analysis of neuroinflammation and signaling pathway in APP/PS1 and WT mice.
Figure 6.
Figure 6.
Correlation analysis of different gut microbiota, metabolites and hub differently expressed genes.
Figure 7.
Figure 7.
FMT intervention regulated glycerophospholipid metabolism and ameliorated Aβ pathology and neuroinflammation in APP/PS1 mice.
Figure 8.
Figure 8.
The diagram of the hypothesis model in this study.
See this image and copyright information in PMC

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