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

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.