The association of aromatic microbial metabolites, inflammatory and autoimmune biomarkers with clinical dynamics in severe diseases of the central nervous system

Abstract

To identify the association between the changes in the profile of microbial metabolites, inflammatory and autoimmune markers and the dynamics of neurological status in chronic critically ill patients with diseases of the central nervous system (CNS). Sixty serum samples from 37 patients, aged 19-77 years, with severe CNS diseases were studied. The changes in clinical condition were assessed with NIHSS, the Rankin scale, the Glasgow Coma Scale, the FOUR Coma Scale and the Rivermead Mobility Index. The levels of aromatic microbial metabolites (AMM) and several inflammatory and autoimmune biomarkers, including the contents of procalcitonin (PCT) and S100, the activity of leukocyte elastase (LE) and a1-proteinase inhibitor a1-PI, the levels of autoantibodies to S100b and MBP were measured. Serum from 60 age- and sex-matched healthy people with no signs of neurological and somatic pathology was used as a control. All patients were divided into groups depending on the neurological dynamics: A - positive (n=16), B - without dynamics (n=15), C - negative (n=6). The study revealed a profile of AMM, as well as inflammatory and autoimmune biomarkers associated with the severity of neurological disorders. A significant increase in acute phase proteins, S-100 level and a decrease in the functional activity of neutrophils (via LE activity) were observed in the serum of patients. The different dynamics of neurological status was associated with the multidirectional changes in the microbial metabolites profile and biomarkers. The correlations between the clinical and biological parameters indicate that AMM might modulate immune reactions in patients with different dynamics of neurological status. The results suggest the involvement of AMM and the level of immune activation via biomarkers in the pathogenesis of neurological dysfunction. Dynamic changes in the profile of microbial metabolites and the level of activation of the immune system may be a promising tool for prediction of neurological recovery.