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.
Keywords: brain-derived neurotrophic factor; catechol-O-methyltransferase; depression; extracellular vesicles; irritable bowel syndrome.
© 2021 John Wiley & Sons Ltd.