The gut microbiota-brain axis in neurological disorders

Abstract

Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota-gut-brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe-based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Keywords: Alzheimer's disease; Parkinson's disease; autism; fecal microbiota transplantation; gut microbiota–brain axis; neurological disorders; probiotics.

FIGURE 1

Bidirectional communication between the gut and the brain. The main communication pathways between microbes and the brain include neural pathways, immune pathways, and metabolic signals. Gut disorders send signals to the brain via the vagus nerve, and a decrease in beneficial bacteria and an increase in proinflammatory bacteria cause altered levels of microbial metabolites, including neurotransmitters, SCFA, and indole metabolites. The deposition of characteristic proteins in neurodegenerative diseases has also been associated with gut microbiota (Aβ in AD; αSyn in PD). These signals stimulate glial cells in the brain, the expression of proinflammatory genes, neuronal loss, synaptic dysfunction, and the rise of proinflammatory cytokines.

FIGURE 2

Therapeutic interventions to modulate the gut microbiota. Supplementation with probiotics and prebiotics (e.g., Bifidobacterium, Lactobacillus, FOS, GOS) regulates gut microbiota, reduces intestinal mucosal injury, inhibits proinflammatory response, and inhibits oxidative reaction. FMT reduces intestinal inflammation, corrects gut disorder, and ameliorates neuroinflammation. Dietary interventions (Mediterranean diet, ketogenic diet, and intermittent fasting) can protective cognitive function, anti‐inflammatory effects, and neuroprotective effects. These therapeutic interventions act on the gut–brain axis through neural, immune, and metabolic signaling pathways to improve gut health and, in turn, neurological disorders progression.