Parkinson’s disease (PD) is a progressive, irreversible neurodegenerative disorder characterized by motor impairments and a wide spectrum of non-motor symptoms, including gastrointestinal dysfunction, sleep disturbances, depression, and cognitive decline. These manifestations arise from disturbances across multiple systems—gastrointestinal, neuroendocrine, immune, enteric, and central nervous systems. Alterations in the gut microbiota may play a causal role in PD onset and frequently accompany disease progression. The gut–brain axis, particularly the vagus nerve, is increasingly recognized as a key communication pathway whose dysregulation contributes to systemic dysfunction and the breakdown of homeostasis, ultimately driving PD pathology. Currently, there is no cure for PD, and existing treatments primarily target symptom relief. Effective management of PD requires a comprehensive approach that integrates multiple pharmacologically active agents aimed at restoring impaired organ functions and, when possible, neutralizing toxic factors that accelerate disease progression. One promising therapeutic avenue lies in functional gut bacteria, which form the basis for developing live biotherapeutic products, postbiotics, and bacterial vesicles. In this review, we summarize current data on the effects of probiotics in PD, drawing on both animal models and clinical studies. We highlight the role of probiotics in modulating PD pathophysiology and discuss their potential as adjunctive therapeutic agents. To provide a broader perspective, we also include sections describing the clinical manifestations of PD, gut microbiota alterations associated with the disease, and the role of artificial intelligence, particularly machine learning, in constructing functional models of PD.

Introduction. Experimental and clinical studies have repeatedly shown the interplay between the intestinal microbiota properties and the nervous system, with a clear link established between changes in microbiota and the development of a neurodegenerative process. It is thought that inflammation and microbiota disturbances provoke the spread of pathological forms of a-synuclein in the nervous system, which is recognized as the main cause of neurodegeneration in Parkinson disease (PD). Aim of the study: to identify the effect of a pharmabiotic based on a Lactobacillus fermentum U-21 strain in Wistar rats with paraquat-induced parkinsonism. Materials and methods. Two groups of animals received intra-abdominal paraquat injections (8 doses of 10 mg/kg, every second day for 15 days) and then received orally either a 0.9% NaCl solution, or the U-21 preparation daily for 15 days. The control groups received 0.9% NaCl injections and either a U-21 preparation, or a 0.9% NaCl solution orally under the same regimen. Motor activity was tested in the open field and narrowing beam walking tests. Changes in tyrosine hydroxylase positive enteric plexus fibers and the in quantity of intestinal villi goblet cells were measured morphologically. Results. Paraquat administration led to a gradual animal death, however, administration of the U-21 increased their survival rate and preserved their motor activity at the level of the control rats. Oral administration of the pharmabiotic only did not alter the animals’ motor activity. Paraquat reduced density of the tyrosine hydroxylase positive fibers and increased the number of goblet cells, while the study drug partially diminished the changes induced by paraquat. Conclusion. The U-21 preparation demonstrated high biological activity in the neurotoxin-induced model of PD, which justifies further, extended studies of its effects.

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.

A single intraperitoneal injection to rats of the mitochondria-targeted plastoquinone antioxidant SkQR1 at dose 1 μmol/kg significantly improved reproduction by the rats of the passive avoidance conditional reflex. In vitro experiments on hippocampal slices showed that a single intraperitoneal injection of SkQR1 24 h before the preparation of the slice significantly increases the synaptic transmission efficiency of the pyramidal neurons of the CA1 field. The findings indicate that SkQR1 has a positive effect on memory processes.