Serum and cerebrospinal fluid neuroinflammatory biomarkers and trimethylamine N-oxide: associations with white matter lesion severity

IntroductionThis study aimed to investigate the association between a multi-panel biomarker profile across the blood-brain barrier and the severity of white matter lesions (WML) in 42 patients [mean age: 60.3 ± 12.1 years; 45.2% male], suggesting a potential inflammatory endotype rather than defining a distinct phenotype due to the cross-sectional design and limited sample size. We assessed the gut-brain axis role in WML pathogenesis through analysis of paired serum and cerebrospinal fluid samples.MethodsIn this cross-sectional clinical study, 42 patients (aged 16–78 years; inclusion of younger subjects was based on radiological confirmation of WML unrelated to acute cerebrovascular events) with radiologically confirmed WML were stratified into four severity groups based on combined Fazekas global score (range 0–3, incorporating both periventricular and deep white matter hyperintensities). Levels of six biomarkers—interleukin-1β (IL-1β), matrix metalloproteinase-2 (MMP-2), tumor necrosis factor-α (TNF-α), trimethylamine N-oxide (TMAO), S100 calcium-binding protein β (S100β), and immunoglobulin G (IgG)—were simultaneously quantified in paired serum and cerebrospinal fluid (CSF) samples using ELISA.