Ivan A. Potapov

Since there is currently no cure for Parkinson’s disease, pharmacobiotic approaches based on gut microbiota—capable of producing pharmacologically active compounds—are under development. In this study, we propose LfU21, derived from the strain Limosilactobacillus fermentum U-21, as a candidate pharmacobiotic. To evaluate its efficacy, a combined LPS- and lactacystin (LAC)-induced Parkinson’s disease model was established in Wistar rats. Effects were assessed using behavioral, biochemical, immunomodulatory, and transcriptomic biomarkers. LfU21 administration reduced α-synuclein levels, altered motor performance in the “Rung ladder” test, and modulated bdnf gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, drd2 and bdnf gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in bdnf expression, and behavioral deficits in the “Open Field” and “Rung ladder” tests, respectively. The multifunctional activity of LfU21 in a combined Parkinson’s disease model underscores its therapeutic potential and helps identify a target patient cohort for future clinical trials.

Since there is no cure for Parkinson's disease yet, pharmacobiotic drugs based on the gut microbiota capable of producing the necessary pharmacologically active compo-nents are being developed. The drug LfU21 based on the strain of Limosilactobacillus fermentum U-21 is proposed as a candidate for pharmacobiotics in this work. To char-acterize the effectiveness of the studied drug, a combined LPS and lactacystin (LAC) induced PD model in the Wistar rat line was used. The analysis was performed using behavioral, biochemical, immune, and transcriptomic biomarkers. LfU21 reduces the level of α-synuclein, changes motor activity in the “Rung ladder” test and the expres-sion of the bdnf gene in both hemispheres of the brain. When exposed to LPS, LfU21 prevents changes in the level of the immune response, GSH, expression of the drd2 and bdnf genes, and the number of goblet cells in the intestine. When exposed to LAC and LAC+LPS, LfU21 prevents an increase in α-synuclein, a decrease in bdnf expression, and indicators in the “Open Field” and “Rung ladder” tests, respectively. The effect of LfU21 in a combined model of Parkinson's disease confirms its multifunctionality. This allows us to determine the cohort of patients for future clinical trials of LfU21.