Parkinson's disease and the gut-brain connection: unveiling pathways, mechanisms and promising therapies.

Parkinson's disease is the second most common neurodegenerative disorder, with a global prevalence of over 6.1 million in 2016, a figure expected to rise with an ageing population. According to recent research findings, the gut-brain axis plays a crucial role in understanding the development of Parkinson's Disease. The Gut-Brain axis establishes communication pathways between gut microbiota, the enteric nervous system, and the CNS through neural, immune and endocrine signals. The gut microbiota regulates neuroinflammatory response, neurotransmitter transmissions and motor dysfunction through its production of short-chain fatty acids, neurotransmitters, and immune system control mechanisms. Through the vagus nerve, the Enteric nervous system links the brain and gut to earning it the designation of the "second brain". Alterations in gut microbiota in PD patients result in increased intestinal permeability, permitting bacterial endotoxins such as lipopolysaccharides to enter the bloodstream and trigger systemic inflammation. This subsequently stimulates microglia and astrocytes in the brain, intensifying neuroinflammation and dopaminergic neuronal degeneration. Furthermore, α-synuclein aggregates originating from the gut transmit to the brain through the vagus nerve, employing a prion-like mechanism that promotes Lewy body pathology. Recent research suggests that probiotics, natural products, and synthetic drugs may restore microbial homeostasis, enhance gut barrier integrity, and modulate neuroinflammatory responses, offering potential therapeutic benefits for Parkinson's disease. Probiotics have been shown to reduce inflammation, improve gut motility, and mitigate α-synuclein pathology. This review underscores the bidirectional interplay between gut and brain, highlighting the potential of gut-centric therapies in mitigating PD pathology and improving patient outcomes.