The gut microbiome, systemic inflammation, and autoimmunity in Parkinson's disease

Dec 13, 2025The Lancet. Neurology

Gut bacteria, body inflammation, and immune problems in Parkinson's disease

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Abstract

Individuals with Parkinson's disease show alterations in gut microbial composition, with reductions in anti-inflammatory taxa and increases in pro-inflammatory bacterial species.

Inflammation is a key characteristic of Parkinson's disease, involving both the central nervous system and systemic immune activation.
Altered gut microbial composition in Parkinson's disease is associated with changes in immune function.
Preclinical studies indicate that changes in the microbiome can promote the aggregation of α-synuclein and increase neuroinflammation.
Human data suggest that the gut and immune system may be involved early in the progression of Parkinson's disease.
Gut microbiome alterations may modulate systemic immune activation through autoreactive T cells, potentially influencing neurodegeneration.

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Inflammation is a core feature of Parkinson's disease, extending beyond the CNS to include systemic immune activation. The gut microbiome is increasingly recognised as a key regulator of immune function in the gastrointestinal tract, peripheral circulation, and brain. In individuals with Parkinson's disease, gut microbial composition is altered, with reductions in anti-inflammatory taxa and increases in pro-inflammatory bacterial species. Preclinical studies have shown that microbiome alterations can promote α-synuclein aggregation and neuroinflammation, whereas human data suggest early involvement of the gut and immune system. Immune-mediated mechanisms in Parkinson's disease include activation of brain resident microglia and peripheral innate and adaptive immune cells. Emerging evidence suggests the gut microbiome modulates systemic immune activation, through autoreactive T cells that might drive neurodegeneration. An improved understanding of how the microbiome shapes inflammation and autoimmunity in Parkinson's disease could inform the development of therapies that target the immune system or the gut-brain axis.