Microbiota dysfunction in patients with brain damage in chronic critical condition

Abstract

In patients with severe brain damage, the severity of the course/outcome of a chronic critical condition is associated with dysfunction of the intestinal microbiota, which can be assessed by the level of microbial metabolites circulating in the blood.The purpose of the study. To establish a connection between the dynamics of a chronic critical condition developed as a result of severe brain damage and microbiota dysfunction.Patients and methods. The study included 83 patients in chronic critical state (CCS) with the consequences of ischemic/ hemorrhagic stroke (n = 34), traumatic brain injury (n = 18), hypoxic brain damage (n = 7), neurosurgical interventions (n = 7), meningitis (n = 3); and 30 healthy people (control group). To assess the neurological status in dynamics, the stroke scales of the National Institutes of Health (NIHSS), the FOUR, Rankin scales, and the Rivermead Mobility Index were used. The taxonomic composition of the microbiota was evaluated by 16S rRNA sequencing and PCR. Biomarkers (by ELISA Kit) and aromatic microbial metabolites (by GC-MS) were monitored twice a week.Results. The peculiarities of the taxonomic composition of the intestinal microbiota in long-term ill patients with brain damage, the predominance of conditionally pathogenic facultative anaerobes (Klebsiella spp., Proteus spp., Staphylococcus aureus) over the pool of strict anaerobes were revealed. The relationship between the dynamics of microbial metabolites in blood and gut of patients with the course and outcome of the disease has been established. Patients with positive clinical dynamics of CCS were characterized by a stable level or decrease in microbial metabolites during treatment. In the group of patients with negative clinical dynamics, an increase in the level of microbial metabolites, especially hydroxylated phenyl carboxylic acids, was revealed.Conclusion. In patients with brain damage, the levels of microbial metabolites circulating in the blood (p-hydroxyphenylacetic, phenyl-lactic, p-hydroxyphenyl-lactic acids) reflect the degree of microbiota dysfunction and the severity of the course of CCS, which is of prognostic importance.