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

📖 Top 20% JournalOct 6, 2025Brain research

Parkinson's Disease and the Gut-Brain Link: Key Pathways, How It Works, and Possible Treatments

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Abstract

Over 6.1 million people globally were affected by Parkinson's disease in 2016, a figure expected to rise with an aging population.

The gut-brain axis facilitates communication between gut bacteria and the brain through various signaling pathways.
Alterations in gut microbiota in Parkinson's disease may lead to increased intestinal permeability, allowing harmful substances to enter the bloodstream.
This increase in permeability could trigger systemic inflammation, which may intensify neuroinflammation and contribute to neuronal degeneration.
Aggregates of α-synuclein from the gut may transmit to the brain via the vagus nerve through a mechanism similar to prion disease.
Probiotics and other treatments may help restore gut health, improve gut barrier function, and reduce neuroinflammation associated with Parkinson's disease.

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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 Central nervous system 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 Parkinson's disease 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 Parkinson's disease pathology and improving patient outcomes.

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