Acupuncture modulates the gut microbiota in Alzheimer's disease: current evidence, challenges, and future opportunities

Abstract

Alzheimer's disease, one of the most severe and common neurodegenerative diseases, has no effective cure. Therefore it is crucial to explore novel and effective therapeutic targets. The gut microbiota - brain axis has been found to play a role in Alzheimer's disease by regulating the neuro-immune and endocrine systems. At the same time, acupuncture can modulate the gut microbiota and may impact the course of Alzheimer's disease. In this Review, we discuss recent studies on the role of acupuncture on the gut microbiota as well current challenges and future opportunities of acupuncture as potential treatment for the prevention and treatment of Alzheimer's disease.

Keywords: Alzheimer’s disease; acupuncture; gut microbiota; inflammation; probiotics.

Figure 1

The relationship between Alzheimer’s disease and the gut microbiota. The brain-gut axis is a two-way communication system between the brain and the gut. The vagus nerve acts as a communication hub to establish a connection between the brain and the gut. The EGCs and TLRs in the intestinal epithelium can work with the vagal nerves to detect changes in gut signals and then complete the transmission of information from the brain to the gut. TLR and PGN in the intestinal environment can act as receptors of the microbial immune response and induce immune responses in various organs, including the brain, via activation of local immunity. Additionally, during AD pathology, gut microbes produce derived products such as SCFAs, LPS and PUFAs, which can permeate the intestinal epithelium and the blood–brain barrier and enter the brain via systemic circulation. This process can influence the polarization of microglia toward a pro-inflammatory direction, activate inflammatory pathways in the brain and upregulate the levels of inflammatory factors, leading to the deposition of pathological products such as A β in the brain. Simultaneously, the heightened inflammatory response in the brain also impacts the gut microbiota, creating a two-way regulation that ultimately triggers AD.

Figure 2

Mechanism of acupuncture in the treatment of Alzheimer’s disease. Acupuncture can affect the messages via the BGM axis to influence AD in the following several ways: (1) Acupuncture can directly (or through the vagus nerve) affect the structure and function of gut microbiota to further reduce intestinal permeability, and may also affect the inflammatory response of the CNS and Aβ expression through this process. (2) Acupuncture can modulate the activation of the HPA axis, which further affects the expression of γ-aminobutyric acid and NYP mRNA to reduce intestinal permeability. (3) Acupuncture can increase the expression of tight-binding proteins in the BBB (such as the expression of ZO-1 and occlusion proteins) to reduce BBB permeability. (4) By modulating the levels of probiotics, acupuncture can affect inflammation in the CNS. The probiotics also can reduce LPS secretion to reduce intestinal permeability. (5) Acupuncture can upregulate BDNF, VE GF, GABA and DA levels to influence neural functional remodeling.