The mechanisms of
coffee against
Parkinson disease (PD) remained incompletely elucidated. Numerous studies suggested that gut microbiota played a crucial role in the pathogenesis of PD. Here, we explored the further mechanisms of
coffee against PD via regulating gut microbiota. C57BL/6 mice were intraperitoneally injected with
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) to induce a PD mouse model, then treated with
coffee for 4 consecutive weeks. Behavioral tests consisting of the pole test and beam-walking test were conducted to evaluate the motor function of mice. The levels of
tyrosine hydroxylase (TH) and α-
synuclein (α-syn) were assessed for dopaminergic neuronal loss. The levels of
occludin,
glial fibrillary acidic protein (GFAP), Bcl-2, Bax, cleaved
caspase-3, and
cytochrome c (Cyt c) were detected. Moreover, microbial components were measured by
16s rRNA sequencing. Our results showed that
coffee significantly improved the motor deficits and TH neuron loss, and reduced the level of α-syn in the
MPTP-induced mice. Moreover,
coffee increased the level of BBB
tight junction protein occludin and reduced the level of astrocyte activation marker GFAP in the
MPTP-induced mice. Furthermore,
coffee significantly decreased the levels of proapoptotic
proteins, including Bax, cleaved
caspase-3, and
cytochrome c, while it increased the level of antiapoptotic
protein Bcl-2, consequently preventing
MPTP-induced apoptotic cascade. Moreover,
coffee improved
MPTP-induced gut microbiota
dysbiosis. These findings suggested that the
neuroprotective effects of
coffee on PD were involved in the regulation of gut microbiota, which might provide a novel option to elucidate the effects of
coffee on PD.