SRP410003 PRJNA905333 Casein Intake Exacerbated Dopaminergic Nerve Injury, Intestinal Inflammation and Gut Microbiota disorder in Recovering MPTP Mice Parkinson's disease (PD) is the fastest-growing neurodegenerative disease around the world, with pathogenic factors and means to halt disease progression being elusive, which places an enormous burden on patients and caregivers. Meanwhile, through the "brain-gut axis", changes in the gut microbiota and metabolites are closely related to the onset and progression of PD. The investigation found that dairy products, especially milk intake, were positively correlated with the occurrence of Parkinson's disease, but the specific mechanisms remain largely unexplored. In this study, the effects of casein (an essential component of milk) intake on dopaminergic nerve injury and intestinal inflammation in recovering PD mice (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced) were investigated. Furthermore, the changes in the gut microbiota and fecal metabolites were analyzed to explore possible mechanisms. Meanwhile, the effects of antibiotics plus casein and casein acid hydrolysate respective intake in these recovering PD mice were also researched in contrast. The results showed that in recovering PD mice, casein reduced motor coordination, led to gastrointestinal dysfunction, impaired dopaminergic neurons, and induced intestinal inflammation. Most importantly, the gut microbiota homeostasis was disturbed by increasing the Firmicutes/Bacteroidetes ratio, decreasing the gut microbiota diversity, and reducing the relative abundance of Candidatus Saccharimonas, Eisenbergiella, and Alistipes. Casein also induced abnormal alterations in fecal metabolites, especially Genistein, L-Methionine, L-Glutamate, Thymine, and S-2-hydroxyglutaric acid, and significantly upregulated both pathways of protein digestion and absorption and central carbon metabolism of cancer. In summary, our results suggested that the damaging effect of casein in recovering PD mice depended on gut microbiota and revealed the effects of casein on gut microbiota and related metabolites. These results will provide new insights into the impact of milk/dairy products on PD progression and supply information on dietary options for PD patients.