Gut-targeted regulatory strategies, such as probiotics, prebiotics and so on, can exert beneficial effects on Alzheimer's disease via the endocrine, neural, metabolic, and immune systems of the microbiota-gut-brain axis.

Modern nutrition is a core element of clinical treatment. Although some literature addresses neuro-nutrition's effects on Alzheimer's disease (AD), a systematic discussion of how the body's six essential nutrients impact AD is lacking. Moreover, neural glial cells directly participate in the pathological regulation of AD. A novel conceptual framework linking "essential nutrients - glial cells - AD" needs to be summarized. Therefore, this review examines the regulatory roles of glial cells (astrocytes, microglia, and their networks) in AD and explores how essential nutrients impact AD via glial cells. Specifically, vitamins (NR, NMN, etc.), minerals (copper, iron, selenium, etc.), proteins and amino acids (arginine, citrulline, methionine, etc.), lipids (fatty acids, phosphatidylinositol, etc.), and carbohydrates (trehalose, oligosaccharides, plant polysaccharides, etc.) can influence important functions such as brain energy metabolism remodeling, inflammatory factor secretion, and phagocytic clearance by regulating microglia and astrocytes. Moreover, a significant strength of this review is its clear exposition of nutrient alterations observed in AD patients, coupled with detailed recommendations for nutritional interventions targeting AD prevention and management. Furthermore, it also investigated beneficial dietary patterns for improving AD. In conclusion, this review explores the "essential nutrients -glial cell" molecular interactions, laying the foundation for precision nutrition-based AD strategies.

Alzheimer’s disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer’s learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.

Cognitive impairment, as a prevalent symptom of nervous system disorders, poses one of the most challenging aspects in the management of brain diseases. Lipids present in the cell membranes of all neurons within the brain and dietary lipids can regulate the cognition and memory function. In recent years, the advancements in gut microbiome research have enabled the exploration of dietary lipids targeting the gut–brain axis as a strategy for regulating cognition. This present review provides an in-depth overview of how lipids modulate cognition via the gut–brain axis depending on metabolic, immune, neural and endocrine pathways. It also comprehensively analyzes the effects of diverse lipids on the gut microbiota and intestinal barrier function, thereby affecting the central nervous system and cognitive capacity. Moreover, comparative analysis of the positive and negative effects is presented between beneficial and detrimental lipids. The former encompass monounsaturated fatty acids, short-chain fatty acids, omega-3 polyunsaturated fatty acids, phospholipids, phytosterols, fungal sterols and bioactive lipid-soluble vitamins, as well as lipid-derived gut metabolites, whereas the latter (detrimental lipids) include medium- or long-chain fatty acids, excessive proportions of n-6 polyunsaturated fatty acids, industrial trans fatty acids, and zoosterols. To sum up, the focus of this review is on how gut–brain communication mediates the impact of dietary lipids on cognitive capacity, providing a novel theoretical foundation for promoting brain cognitive health and scientific lipid consumption patterns.