Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's Disease

• Published in: Movement disorders Vol. 33; no. 5; pp. 793 - 804
• Main Authors: Houser, Madelyn C., Chang, Jianjun, Factor, Stewart A., Molho, Eric S., Zabetian, Cyrus P., Hill‐Burns, Erin M., Payami, Haydeh, Hertzberg, Vicki S., Tansey, Malú G.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2018
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis; Angiogenesis Inducing Agents - metabolism; biomarker; Body mass index; C-Reactive Protein - metabolism; Cytokines; Cytokines - metabolism; Feces - chemistry; Female; Gastroenteritis - etiology; Gastroenteritis - metabolism; Humans; Inflammation; Intestine; Male; Metadata; Middle Aged; Mood Disorders - etiology; Movement disorders; Multivariate analysis; Neurodegenerative diseases; Parkinson Disease - complications; Parkinson Disease - psychology; Parkinson's disease; Probiotics; Sex Characteristics; Sex differences; Smoking; stool; Vascular endothelial growth factor; stool; Parkinson's disease; intestine; biomarker; inflammation
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.27326

Background: Gastrointestinal symptoms are common in Parkinson's disease and frequently precede the development of motor impairments. Intestinal inflammation has been proposed as a driver of disease pathology, and evaluation of inflammatory mediators in stool could possibly identify valuable early‐stage biomarkers. We measured immune‐ and angiogenesis‐related proteins in human stool to examine inflammatory profiles associated with Parkinson's disease. Methods: Stool samples and subjects' self‐reported metadata were obtained from 156 individuals with Parkinson's disease and 110 without, including spouse and nonhousehold controls. Metadata were probed for disease‐associated differences, and levels of 37 immune and angiogenesis factors in stool homogenates were measured by multiplexed immunoassay and compared across experimental groups. Results: Parkinson's disease patients reported greater incidence of intestinal disease and digestive problems than controls. Direct comparison of levels of stool analytes in patients and controls revealed elevated vascular endothelial growth factor receptor 1, interleukin‐1α, and CXCL8 in patients' stool. Paired comparison of patients and spouses suggested higher levels of multiple factors in patients, but this was complicated by sex differences. Sex, body mass index, a history of smoking, and use of probiotics were found to strongly influence levels of stool analytes. Multivariate analysis accounting for these and other potential confounders confirmed elevated levels of interleukin‐1α and CXCL8 and also revealed increased interleukin‐1β and C‐reactive protein in stool in Parkinson's disease. These differences were not dependent on subject age or disease duration. Conclusions: Levels of stool immune factors indicate that intestinal inflammation is present in patients with Parkinson's disease. © 2018 International Parkinson and Movement Disorder Society