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

## TL;DR

This study uses advanced imaging to show gut inflammation linked to Parkinson’s and IBD, suggesting immune dysfunction starts in the gut.

## Contribution

The study introduces spatial single-cell multiomics to reveal immune dysfunction in peripheral tissues in Parkinson’s and IBD.

## Key findings

- Inflammatory injury in gut epithelial cells is linked to iron mishandling in both PD and IBD.
- Parallel RNA and protein dysregulation in gut epithelium is observed in PD and IBD samples.
- CCL22 protein depletion in plasma (PD) and stool (IBD) suggests systemic immune dysfunction.

## Abstract

Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2–4. We investigated peripheral relationships that may underlie mechanisms along the gut–blood axis that contribute to PD progression. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized and identified inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be one catalyst that primes circulating immune cells to body-first PD progression.