Modulation of Behavioral, Biochemical, Immunomodulatory, and Transcriptional Profiles by the Strain Limosilactobacillus fermentum U-21 in Combined Model of Parkinson’s Disease in Wistar Rats

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 <i>Limosilactobacillus fermentum</i> 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 <i>bdnf</i> gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, <i>drd2</i> and <i>bdnf</i> gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in <i>bdnf</i> 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.