Gut-brain axis – new horizons in movement disorders

Abstract

The gut–brain axis is a bidirectional communication system that connects the enteric nervous system of the gastrointestinal tract to the central nervous system. Understanding the complex mechanisms of action of this axis is essential for investigating the pathophysiological processes involved in the development of various neurological and gastrointestinal disorders. The enteric nervous system is composed of an extensive network of neurons distributed throughout the gastrointestinal tract. Although it functions relatively independently of the central nervous system, it is responsible for the regulation of key gastrointestinal processes, including peristalsis, intestinal motility, secretion, and absorption of nutrients, acting as an autonomic regulator of gastrointestinal functions. The vagus nerve is the primary neural pathway connecting the gut and the brain and is composed of afferent (sensory) and efferent (motor) fibres. Afferent fibres transmit information from the gut to the brain, including signals related to satiety, nutrient availability, and gastrointestinal discomfort. Efferent fibres transmit impulses from the brain to the digestive system, modulating functions such as gastric secretion and intestinal motility. This two-way communication allows for continuous regulation and maintenance of homeostasis between the gut and the brain. The gut microbiota comprises a diverse community of microorganisms, including bacteria, viruses, and fungi, that colonize the gastrointestinal tract, with their numbers exceeding the number of human cells in the body. The microbiota participates in numerous metabolic processes, including enzymatic activity, synthesis of vitamins and other bioactive metabolites, and inhibition of pathogen growth. Furthermore, it influences neuronal signalling, immune activity, and metabolic balance through the production of neuroactive molecules, such as neurotransmitters, short-chain fatty acids (SCFAs), and cytokines. Dysbiosis refers to a disruption of the balance of the gut microbiota, characterized by a reduction in bacterial diversity and changes in the composition of the microbial community, which can lead to pathological modulation of the immune response, including changes in cytokine expression and activity. Most research on the role of the gut–brain axis in movement disorders has been conducted in the context of the pathophysiology of Parkinson's disease. Parkinson's disease is a progressive neurodegenerative disorder characterized primarily by the loss of dopaminergic neurons in the substantia nigra, leading to characteristic motor symptoms, including tremor, rigidity, and bradykinesia. However, early non-motor symptoms, such as constipation and other bowel dysfunction, often occur several years before the onset of motor manifestations, suggesting that changes in gut function and microbiota may precede neurodegeneration. Therapeutic approaches aimed at modulating the gut–brain axis, particularly the gut microbiota and enteroendocrine cells, represent a potential strategy for slowing disease progression or even preventing its onset. Prominent among such approaches are the use of prebiotics and probiotics, fecal microbiota transplantation, short-chain fatty acid supplementation, and glucagon-like peptide-1 receptor agonists, which have entered advanced stages of clinical trials.