Modulation of Behavioral, Biochemical, Immunomodulatory, and Transcriptional Profiles by the StrainU-21 in Combined Model of Parkinson's Disease in Wistar Rats.

Abstract

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 strainU-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 modulatedgene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels,andgene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline inexpression, 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.