Spatial single-cell multiomics reveals peripheral immune dysfunction in Parkinson’s and inflammatory bowel disease
Year: 2026
Type: article
Study design: Observational Study
Abstract: Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world 1 . Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD 2–4 . 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.
Source: npj Parkinson s Disease
Authors: MacKenzie L. Bolen, Marc Buendia, Ji Shi, Hannah Staley, Jennifer M. Kachergus, Philip A. Efron, Gwoncheol Park, Ravinder Nagpal, Stephan D. Alvarez, Qing-Shan Xue, Nikolaus R. McFarland, Ellen M. Zimmermann, Christopher E. Forsmark, Kelly B. Menees, Azucena Salas, E. Aubrey Thompson, Malú Gámez Tansey
Institutions: University of Florida Health, University of Florida, Aligning Science Across Parkinson's, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Mayo Clinic in Florida, Mayo Clinic Comprehensive Cancer Center (Florida), Florida State University, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: Michael J. Fox Foundation for Parkinson's Research, Parkinson's Foundation, Aligning Science Across Parkinson’s, Ministerio de Ciencia e Innovación, National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G2025142915, Role of central and peripheral immune crosstalk in FTD-Grn neurodegeneration, G315848923, Role of Gut Inflammation and Immunity on Proteostasis, Noradrenergic Degeneration and AD risk, G5821074941, G6892736131, Pathological Myeloid Activation After Sepsis and Trauma, Role of central and peripheral immune crosstalk in FTD-Grn neurodegeneration
OpenAlex ID: W7124508321