Posted by The role of gut in development of Parkinson’s disease has been long suspected as constipation appears years before the typical symptoms, muscle stiffness and tremor are observed. By using animal models and profiling human microbiomes, researchers uncover the molecular mechanisms and microbial species that may contribute to Parkinson’s disease, leading to potential gut-targeted therapies.
In Parkinson’s disease, alpha-synuclein proteins form aggregates in neurons in the brain. Dopaminergic neurons are particularly vulnerable to alpha-synuclein build up, and their progressive loss is one of the hallmarks of the disease. While both genetics and environmental aspects contribute to Parkinson’s disease, no one combination of factors causes the disease.
Numerous studies profiling the gut microbiome noted clear differences between the microbiome composition in healthy people versus people with Parkinson’s disease. But some of the strongest evidence linking the gut microbiome to Parkinson’s disease arose when Mazmanian and his team studied a mouse model of Parkinson’s disease that overexpresses alpha-synuclein in its neurons (1). When Mazmanian’s team depleted the gut microbes from Parkinson’s disease mouse models, the animals’ motor functions improved, and they had decreased alpha-synuclein aggregates and neuroinflammation in their brains. Then when the researchers transplanted microbiomes from humans with Parkinson’s disease or heathy controls into their mouse models, the mice with the human Parkinson’s disease microbiome showed worse motor symptoms.
Some fiber a day keeps Parkinson’s disease away
Eating a high fiber diet has all kinds of beneficial effects. Fiber promotes good bowel health, helps maintain blood sugar levels, and reduces cholesterol levels, just to name a few. It turns out that a high fiber diet also associates with a decreased risk for Parkinson’s disease (2).
Mazmanian and his team fed mice overexpressing alpha-synuclein a high fiber diet for 17 weeks. When they compared the microbiomes, the alpha-synuclein overexpressing mice fed the high fiber diet had microbiomes that looked more similar to healthy ones (3). The mice also had improved motor abilities and reduced alpha-synuclein aggregates and microglial activation in the brain.
Can alpha-cyclodextrin, a soluble fiber delay the unset of symptoms in Parkinson disease?
It is generally accepted that alpha-CD reduce postprandial glucose and insulin in blood. The native CDs modulate the bacterial composition of microbiome in the gut. The research on CDs in Parkinson’s disease concentrate on the benfitial effect of HPBCD, a cholesterol sequestering agent. What if alpha-CD, a soluble fiber can be also benefitial?
References
Timothy R. Sampson, Justine W. Debelius, Taren Thron, Stefan Janssen, Gauri G. Shastri, Zehra Esra Ilhan, Collin Challis, Catherine E. Schretter, Sandra Rocha, Viviana Gradinaru, Marie-Francoise Chesselet, Ali Keshavarzian, Kathleen M. Shannon, Rosa Krajmalnik-Brown, Pernilla Wittung-Stafshede, Rob Knight, Sarkis K. Mazmanian (2016) Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell 167, 469-1480.e12. https://doi.org/10.1016/j.cell.2016.11.018.
Maria I. Maraki, Mary Yannakoulia, Maria Stamelou, Leonidas Stefanis, Georgia Xiromerisiou, Mary H. Kosmidis, Efthimios Dardiotis, Georgios M. Hadjigeorgiou, Paraskevi Sakka, Costas A. Anastasiou, Eleni Simopoulou, Nikolaos Scarmeas Mediterranean diet adherence is related to reduced probability of prodromal Parkinson’s disease (2019) Move,ment Disorders 34, 48-57.
https://doi.org/10.1002/mds.27489
Reem Abdel-HaqJohannes CM SchlachetzkiJoseph C BoktorThaisa M Cantu-JunglesTaren ThronMengying ZhangJohn W BostickTahmineh KhazaeiSujatha ChilakalaLivia H MoraisGreg HumphreyAli KeshavarzianJonathan E KatzMatthew ThomsonRob KnightViviana GradinaruBruce R HamakerChristopher K GlassSarkis K Mazmanian (2022) A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice eLife 11:e81453. https://doi.org/10.7554/eLife.81453.sa0