The intricate microbial–gut–brain axis in Alzheimer's disease: a review of microbiota-targeted strategies

Abstract

The microbiome–gut–brain axis (MGBA) has emerged as a potential focus for the enhancement of cognitive abilities and the improvement of Alzheimer's disease (AD). Probiotics and prebiotics can improve the imbalance of gut microbiota to alleviate AD symptoms. Current research on probiotics/prebiotics and brain function mainly focuses on metabolic pathways such as those involving microbial metabolites like lipopolysaccharides and short-chain fatty acids, as well as immune pathways that regulate inflammation in the gut and brain. However, the roles played by endocrine and neural pathways remain less explored and warrant further attention. This review explores the intricate mechanisms of gut–brain communication within the MGBA, and especially systematically elaborates on the specific mechanisms of the endocrine pathway (impact of gut-derived and exogenous hormones on brain function) and the neural pathway (regulation of brain function by the sympathetic and parasympathetic systems). It also emphasizes the specific changes in gut microbiota noted in individuals with AD. Additionally, it examines the beneficial effects of probiotics, prebiotics, synbiotics, and postbiotics for cognitive function, reviewing their advancements in preclinical research, clinical trials, and commercial applications. Furthermore, this review delves into novel gut microbiota-related strategies to promote brain health, including antibiotics, certain gut-targeted inhibitors or agonists, fecal microbiota transplantation, whole microbiome transplantation, viral microbiota transplantation, genetically engineered bacteria, and bacteriophage-based in situ intestinal microbiome engineering. Ultimately, this review aims to advance the therapeutic application of gut microbiota-targeted strategies in AD.