This review links Parkinson's disease biology to gut-microbiota regulation of tryptophan metabolism.
Evidence
This review synthesizes research on the , tryptophan's indole, kynurenine, and serotonin pathways, and their possible roles in gastrointestinal function, inflammation, and Parkinson's disease processes.
Caveat
As a review of mechanistic and associative evidence, it does not prove that microbiota-driven tryptophan changes cause Parkinson's disease or that targeting them is therapeutic.
Simplified
Parkinson's disease, a common neurodegenerative disorder in the elderly, is characterized by motor symptoms and non-motor symptoms such as anxiety, depression, sleep disturbances, and gastrointestinal dysfunction, highlighting its nature as a multisystem disease. The critical role of the in maintaining human homeostasis is well established, and growing evidence links its dysfunction and gut microbiota to Parkinson's disease. Communication between the microbiota and the brain occurs through various pathways, including the vagus nerve, intestinal hormonal signals, the immune system, tryptophan metabolism, and microbial metabolites. Among these, tryptophan metabolism is a key metabolic pathway. As an essential amino acid that animal cells cannot synthesize, tryptophan and its metabolites in the intestine depend entirely on dietary intake and gut microbiota production. In the gastrointestinal tract, tryptophan metabolism occurs via three main pathways-the indole pathway, the kynurenine pathway, and the serotonin pathway-all directly or indirectly regulated by gut microbiota. These metabolites are vital in mediating the 'microbiota-gut-brain' dialogue and regulating gastrointestinal functions. Additionally, some metabolites mediate central nervous system inflammation and contribute to neurodegenerative disease processes as aromatic hydrocarbon receptor ligands. This review examines recent research on gut microbiota and host tryptophan co-metabolism and their roles in the development of Parkinson's disease. Furthermore, it explores how targeting gut microbiota and modulating tryptophan metabolism could offer potential therapeutic approaches for Parkinson's disease.
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Gut-Brain Axis