Spatial single-cell multiomics reveals peripheral immune dysfunction in Parkinson's and inflammatory bowel disease

Area of Science:

• Neuroscience
• Gastroenterology
• Immunology

Background:

• Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder globally.
• Gastrointestinal (GI) dysfunction is prevalent in PD, often preceding motor symptoms.
• The gut-blood axis is increasingly recognized for its role in PD pathogenesis.

Purpose of the Study:

• To investigate peripheral mechanisms along the gut-blood axis in PD progression.
• To identify cellular and molecular links between gut health and PD.
• To explore the role of iron metabolism and inflammation in PD.

Main Methods:

• Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue.
• Analysis of RNA and protein expression in gut epithelial cells.
• Assessment of plasma and stool protein levels (CCL22).

Main Results:

• Inflammatory injury and iron mishandling identified in epithelial cells of PD and inflammatory bowel disease (IBD) samples.
• Parallel cross-modal dysregulation of RNA and protein in the gut epithelium in both PD and IBD.
• Depletion of CCL22 protein observed in PD plasma and IBD stool samples.

Conclusions:

• Iron mishandling in the gut barrier likely contributes to systemic inflammation.
• Systemic inflammation may prime immune cells, facilitating body-first PD progression.
• Gut epithelial dysfunction is a key factor in PD pathogenesis.