Enterococcus hirae QT4713-derived dopamine ameliorates intestinal inflammation and MPTP-induced Parkinson’s disease in mice

Gut microbiota dysbiosis regulates Parkinson’s disease (PD) pathology by altering dopamine metabolism in the brain and gut. Although probiotics and other functional strains offer new strategies to enhance host health via the microbiome-gut-brain axis, few naturally occurring gut microbes have shown potential for PD treatment. A strain of Enterococcus hirae QT4713 (QT4713) was isolated from the low-pressure and oxygen environment of the Qinghai-Tibet region at an altitude of 4713 meters. Whole-genome sequencing revealed that QT4713 carried a typical tyrosine decarboxylase gene (TyrDc), enabling the conversion of L-tyrosine into dopamine in vitro. QT4713 enhances antioxidant enzyme activity, reduces inflammatory factor levels, increases the relative abundance of Prevotella and Lachnospiraceae, and promotes short-chain fatty acids (SCFAs) production in mice. Notably, QT4713 significantly enriched the L-tyrosine metabolic pathway, elevating L-dopa and dopamine in the colon and feces while improving the motor performance of mice. An MPTP-induced PD mouse model was used to assess the therapeutic potential of QT4713. Remarkably, QT4713 alleviated motor and gastrointestinal dysfunction (e.g., constipation), mitigated histopathological alterations in the colon and brain, and reduced inflammation and oxidative damage in PD mice. These findings indicate that QT4713 can mitigate motor dysfunction, gastrointestinal disturbances, and dopaminergic neuron loss in PD mice, potentially by increasing dopamine levels through its intrinsic enzymatic activity and by modulating the intestinal microbiota.