Neuronal‐enriched extracellular vesicles in individuals with IBS: A pilot study of COMT and BDNF

Background Irritable bowel syndrome (IBS) is characterized by abdominal pain, bowel habit alterations, and psychiatric comorbidities. Although pathophysiology remains incompletely understood, prior work demonstrates associations with brain‐derived neurotrophic factor (BDNF) and catechol‐O‐methyltransferase (COMT). The purpose of this study was to quantify BDNF and COMT in plasma and in neuronal‐enriched extracellular vesicles (nEVs), assess relationships with psychological symptoms, and gain insight on the brain‐gut connection in IBS. Methods Clinical data and biorepository samples from a parent investigation were used, including scores on the Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES‐D). Distinct subpopulations of nEVs were isolated using neural cell adhesion molecule L1CAM; levels of COMT, mature BDNF, and pro‐BDNF were quantified in plasma and in nEVs using ELISA. Key Results Data from 47 females (28.11 ± 6.85 years) included 18 IBS and 29 healthy control (HC) participants. IBS participants displayed reduced plasma levels of mature BDNF compared with HC (p = 0.024). Levels of COMT plasma and IBS grouping significantly predicted CES‐D scores (p = 0.034). Exploratory analyses by IBS subtype and race revealed African American HC display lower levels of COMT EV than Caucasian HC (p = 0.022). Conclusions & Inferences Lower levels of mature BDNF in IBS participants, preliminary patterns detected in cargo content of nEVs, and relevance of COMT and IBS status to CES‐D scores, offer insight on depressive symptomatology and brain‐gut dysregulation in IBS. Lower COMT levels in nEVs of African Americans highlight the relevance of race when conducting such analyses across diverse populations. Significant differences were detected in plasma levels of mature BDNF between females with IBS and HC, and levels of COMT in nEVs between African American and Caucasian HC. Results offer insight on depressive symptomatology and brain‐gut dysregulation in IBS and highlight the relevance of race when conducting such analyses.