Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer's Disease: A Systematic Review

Abstract

Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, β-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.

Figure 1.

Schematic representation of the mechanisms involved in the crosstalk between the gut microbiota and brain. Abbreviations: CNS = central nervous system, ANS = autonomic nervous system, ENS = enteric nervous system, LPS = lipopolysaccharide, TMAO = trimethylamine N-oxide, and SCFAs = short-chain fatty acids.

Figure 2.

Role of TMAO in the development of Alzheimer’s disease. TMAO can increase central nervous system inflammation, β-amyloid protein, and tau protein accumulation. Tau protein in cerebrospinal fluid is closely related to TMAO, and it can increase oxidative stress and damage mitochondrial function, resulting in cognitive impairment. TMAO = trimethylamine N-oxide.

Figure 3.

Mechanism of bacteria-derived amyloid protein in inflammation regulation in Alzheimer’s disease. NLRP3: NOD-like receptor protein 3.

Figure 4.

Effect of gut microbiota on immune cells in Alzheimer’s disease. Intestinal dysbacteriosis can activate microglia and promote Th1 cell infiltration. It makes these two interact with M1 microglia locally, triggering the differentiation of microglia to a pro-inflammatory state, resulting in cognitive impairment.

Figure 5.

Different prebiotic therapies and their effects on gut microbiota and brain function. Aged rats treated with VSL3 decreased the microglial activation and pro-inflammatory factors production and increased the activity of M2 macrophages. It also showed increased expression of genes related to inflammation and neuronal remodelings, such as BDNF and synaptophysin, decreased oxidative stress, and improved cognitive function. SLAB51 can reduce the pro-inflammatory cytokine, p-AMPK, and p-Akt levels in AD mice, decrease the p-tau level in the brain of mice, and improve their cognitive function. BDNF = brain-derived neurotrophic factor.