D-mannose alleviates rotenone-induced PD mouse model through microbiota-gut-brain axis

Parkinson’s disease (PD) is the second most common neurological degenerative disease in the elderly. Disruption of gut-brain axis crosstalk has been shown to be associated with the pathogenesis of PD. Although drug treatments for PD have been in development for decades, there is currently no drug or therapy that can completely cure PD. Therefore, there is an urgent need to discover new drugs to develop effective PD treatment strategies. D-mannose is a natural, bioactive monosaccharide that is a popular nutritional and health-beneficial food supplement worldwide. However, whether it has a neuroprotective effect on PD is still unclear. C57BL6/J mice aged 8–9 weeks were orally administrated with rotenone solution once a day for four weeks and drinking D-mannose for the following 2 weeks. Fresh fecal pellets from each mouse were used for 16 S rRNA sequencing. We found that D-mannose treatment alleviated motor symptoms, gastrointestinal dysfunctions in rotenone-induced PD mice. 16 S rRNA sequencing found that microbiota alterations were reversed by D-mannose in rotenone-induced PD mice. D-mannose treatment suppressed neuroinflammation by TLR4/MyD88/NF-κB pathway in the SN. This study proved that the importance of D-mannose on PD, and explored the potential mechanism of gut-brain axis in PD pathogenesis, providing a new target for clinical treatment of PD.