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

Oct 14, 2025Food & function

The complex gut-brain connection in Alzheimer's disease and possible treatments targeting gut microbes

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Abstract

Probiotics and prebiotics may alleviate Alzheimer's disease symptoms by improving gut microbiota balance.

The microbiome-gut-brain axis is a potential target for enhancing cognitive abilities and addressing Alzheimer's disease.
Current research highlights the importance of microbial metabolites and immune pathways in gut and brain interactions.
Less attention has been given to the roles of endocrine and neural pathways in gut-brain communication.
Specific changes in gut microbiota have been noted in individuals with Alzheimer's disease.
Various gut microbiota-related strategies, including fecal microbiota transplantation and genetically engineered bacteria, are being explored for their potential to promote brain health.

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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-basedintestinal microbiome engineering. Ultimately, this review aims to advance the therapeutic application of gut microbiota-targeted strategies in AD. in situ

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

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