Spatial single-cell multiomics reveals peripheral immune dysfunction in Parkinson's and inflammatory bowel disease.
Spatial single-cell multiomics reveals peripheral immune dysfunction in Parkinson's and inflammatory bowel disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
US · Author affiliation · country only
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, USA.Location evidence
Barcelona, ES · Author affiliation
University of Barcelona, Gran Via de les Corts, 08007, Barcelona, Spain.Location evidence
Les Corts, ES · Author affiliation
University of Barcelona, Gran Via de les Corts, 08007, Barcelona, Spain.Location evidence
Centro, ES · Author affiliation
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.Location evidence
Tallahassee, US · Author affiliation
The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Sciences, Florida State University, Tallahassee, FL, USA.Location evidence
Norman, US · Author affiliation
Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA.Location evidence
Indianapolis, US · Author affiliation
Department of Neurology, Stark Neuroscience Research Institute, School of Medicine, Indiana University, Indianapolis, IN, USA.Location evidence
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Original 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.