Polymannuronic acid prebiotic plus Lacticaseibacillus rhamnosus GG probiotic as a novel synbiotic promoted their separate neuroprotection Parkinson's disease

Gut microbiota (GM) dysbiosis plays key roles in aggravating Parkinson's disease (PD) and discovery of agents targeting GM may open new avenues for PD therapy. This study aims to investigate the potentially neuro-protective effects and underlying mechanisms of polymannuronic acid (PM) or Lacticaseibacillus rhamnosus GG (LGG), or their combination in a chronic PD mice model. Our results found oral administration of prebiotic PM or LGG separately or in combination for 5 weeks could prevent dopaminergic neuronal loss via improving reduced walking distance and activity or weakened muscle strength in behavior tests by enhancing tyrosine hydroxylase (TH) gene and/or protein expressions in the midbrain and striatum of PD mice. Strikingly, PM and LGG in combination had a much better neuroprotective effects than separate PM or LGG. PM provided neuroprotection via a short chain fatty acids (SCFAs)-mediated anti-inflammation and anti-apoptosis mechanism. The neuro-protective effects of LGG might be associated with its ability to improve the expression of striatal glial cell-derived neurotrophic factor (GDNF) and to increase bacteria abundance of Clostridiales. When PD mice were administered with PM + LGG, PM as prebiotic favored bacterial growth (from Bacilli class to Lactobacillus genus) in the colon, which helped to improve blood brain barrier (BBB) integrity and increase brain-derived neuro-trophic factor (BDNF) and GDNF expressions, thereby inhibiting apoptosis in the striatum. In conclusion, PM and LGG in combination promoted their separate neuroprotection against PD. Our study discovered and testified a novel synbiotic that might be one of the ideal oral agents for PD therapy.

Automated summary

This study discovered that the combination of polymannuronic acid (PM) and Lacticaseibacillus rhamnosus GG (LGG) provided neuroprotection in a chronic Parkinson's disease (PD) mice model. PM exerted neuroprotection through a short chain fatty acids (SCFAs)-mediated anti-inflammation and anti-apoptosis mechanism, while LGG may improve the expression of striatal glial cell-derived neurotrophic factor (GDNF) and increase the abundance of Clostridiales bacteria. The combination of PM and LGG showed better neuroprotective effects than using PM or LGG alone.