Fecal microbiota from patients with Parkinson's disease intensifies inflammation and neurodegeneration in A53T mice

Abstract

Aims

We evaluated the potential of Parkinson's disease (PD) fecal microbiota transplantation to initiate or exacerbate PD pathologies and investigated the underlying mechanisms.

Methods

We transplanted the fecal microbiota from PD patients into mice by oral gavage and assessed the motor and intestinal functions, as well as the inflammatory and pathological changes in the colon and brain. Furthermore, 16S rRNA gene sequencing combined with metabolomics analysis was conducted to assess the impacts of fecal delivery on the fecal microbiota and metabolism in recipient mice.

Results

The fecal microbiota from PD patients increased intestinal inflammation, deteriorated intestinal barrier function, intensified microglia and astrocyte activation, abnormal deposition of α‐Synuclein, and dopaminergic neuronal loss in the brains of A53T mice. A mechanistic study revealed that the fecal microbiota of PD patients stimulated the TLR4/NF‐κB/NLRP3 pathway in both the brain and colon. Additionally, multiomics analysis found that transplantation of fecal microbiota from PD patients not only altered the composition of the gut microbiota but also influenced the fecal metabolic profile of the recipient mice.

Conclusion

The fecal microbiota from PD patients intensifies inflammation and neurodegeneration in A53T mice. Our findings demonstrate that imbalance and dysfunction in the gut microbiome play significant roles in the development and advancement of PD.

Abstract

FMT from PD patients altered the structure and composition of the gut microbiota in recipient mice and significantly altered the metabolic profiles, which collectively may aggravate intestinal and systemic inflammation, cause BBB damage, and eventually lead to dopaminergic neurodegeneration. In conclusion, our results suggest that gut microbiota and intestinal ecological disorders are important driving factors for the progression of PD.