The gut microbiota is continuously influenced by environmental factors and lifestyle habits, and interacts with various organs that affect the host's physiological functions. Recent studies have shown that the microbiota-gut-brain (MGB) axis facilitates bidirectional communication between the enteric nervous system and central nervous system. The brain is rich in lipids, and lipid metabolism is essential for maintaining physiological functions. Therefore, strict regulation of lipids and lipid metabolism is crucial for maintaining brain cell homeostasis. However, studies on the correlation between gut microbiota dysbiosis and lipid imbalance in Alzheimer’s disease (AD) is still insufficient. In this study, we performed 16S rRNA sequencing using fecal samples from AD model mice, confirming a decrease in the probiotics Bifidobacterium and Lactobacillus. Similarly, an imbalance in probiotics is observed in patients with AD. Additionally, we confirmed the dysregulated gene expression of LPC-related metabolic factors and LPA receptors (LPARs) by transcriptomic analysis from AD patients and mouse model. Furthermore, LPA treatment reduced neuroinflammation with diverse cytokines and pathological aggregation of tau with phosphorylation. Taken together, we suggest that gut microbiota dysbiosis in AD may alleviate the pathological features through LPA-mediated lipid metabolism.