# 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

## TL;DR

This study explores a new probiotic candidate, LfU21, which may help treat Parkinson’s disease by improving brain and gut health in rats.

## Contribution

The study introduces LfU21 as a novel pharmacobiotic with potential therapeutic effects in a combined Parkinson’s disease model.

## Key findings

- LfU21 reduced α-synuclein levels and modulated bdnf gene expression in rat striata.
- LfU21 prevented immune response alterations and preserved intestinal goblet cell counts under LPS exposure.
- LfU21 mitigated behavioral deficits and α-synuclein rise in LAC and LAC + LPS groups.

## 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 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.