Paraprobiotics attenuate oxidative stress, dopaminergic neuron loss, and gut microbiome imbalance in an intranasal MPTP rat model of Parkinson's disease

Intestinal dysbiosis may contribute to the progression of Parkinson's disease (PD) by promoting inflammation and oxidative stress. Paraprobiotics, defined as non-viable microbial cells, have emerged as a promising therapeutic strategy. This study evaluated the neuroprotective, gastroprotective, and microbiota-modulating effects of a paraprobiotic blend comprising Lactobacillus casei CCT 7859, Bifidobacterium lactis CCT 7858, and Streptococcus thermophilus ATCC 19258 in a murine PD model induced via intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Seventy female Wistar rats received either intranasal MPTP or saline, followed 24 hours later by 14 days of paraprobiotic treatment (100 mg/kg/day, intragastrically). Fecal and tissue samples were collected for microbiota, oxidative stress, dopaminergic neurodegeneration, and physiological parameter analyses. Antioxidant enzymes (superoxide dismutase and catalase), oxidative damage markers (malondialdehyde, reactive oxygen and nitrogen species), gut microbiota composition, immunohistochemistry for tyrosine hydroxylase, and physiological variables such as body weight, intestinal length, fecal water content, and ash levels were assessed. Paraprobiotic administration enhanced antioxidant defenses, reduced oxidative damage in brain and intestinal tissues, preserved dopaminergic neurons within the nigrostriatal pathway, improved fecal hydration (indicating constipation relief), and decreased fecal mineral content, suggesting improved nutrient absorption. Notably, modulation of gut microbiota, including an increased abundance of beneficial families (Lactobacillaceae and Sutterellaceae) and a reduced abundance of potentially harmful families (Clostridiaceae and Peptostreptococcaceae), may have contributed to oxidative stress attenuation, preservation of gut health, and prevention of dopaminergic neuron loss. Collectively, these findings suggest that paraprobiotics may modulate microbiota composition and oxidative stress in both intestinal and brain tissues, and may attenuate dopaminergic neurodegeneration in an experimental model of PD.