Gastrointestinal disorders in Parkinson's disease and other Lewy body diseases

Parkinson's disease (PD) is pathologically characterized by the abnormal accumulation of alpha-synuclein fibrils (Lewy bodies) in the substantia nigra and other brain regions, although the role of Lewy bodies remains elusive. Constipation usually precedes the motor symptoms in PD, which is in accordance with the notion that alpha-synuclein fibrils start from the intestinal neural plexus and ascend to the brain in at least half of PD patients. The gut microbiota is likely to be involved in intestinal and brain pathologies. Analyses of the gut microbiota in PD, rapid-eye-movement sleep behavior disorder, and dementia with Lewy bodies suggest three pathological pathways. First, Akkermansia, which is increased in PD, degrades the intestinal mucus layer and increases intestinal permeability, which triggers inflammation and oxidative stress in the intestinal neural plexus. Second, decreased short-chain fatty acids (SCFAs)-producing bacteria in PD reduce the number of regulatory T cells. Third, SCFAs also aggravate microglial activation with an unelucidated pathway. In addition, in dementia with Lewy bodies (DLB), which is another form of alpha-synucleinopathies, increased genera, Ruminococcus torques and Collinsella, may mitigate neuroinflammation in the substantia nigra by increasing secondary bile acids. Interventions for the gut microbiota and their metabolites may potentially delay or mitigate the development and progression of PD and other Lewy body diseases.

Automated summary

Parkinson's disease (PD) is characterized by the accumulation of alpha-synuclein fibrils (Lewy bodies) in the brain, starting from the intestinal neural plexus. The gut microbiota plays a role in intestinal and brain pathologies, with increased Akkermansia degrading the intestinal mucus layer and reducing regulatory T cells, while decreased short-chain fatty acids (SCFAs) contribute to microglial activation. In dementia with Lewy bodies (DLB), specific genera may mitigate neuroinflammation. Modulating the gut microbiota and its metabolites may have potential therapeutic effects for PD and Lewy body diseases.