20th International Congress of The Polish Pharmacological Society
The Gut-Brain Axis and urolithins – opportunities for a novel approach to neuroprotection in Parkinson’s disease
The gut-brain axis consists of bidirectional communication between the intestinal environment and the central nervous system, which relies on neuro-immune interactions. Pathological conditions in gut microbiota are suggested to contribute to the development of neurodegenerative diseases as they may initiate impairment of the gastrointestinal mucosal barrier, inducing a systemic inflammatory response in neural cells, leading to the degeneration of these neurons. Moreover, the dysbiosis has been recently suggested to trigger an initial event of misfolding of proteins in the gut. It is hypothesized that synucleinopathy may originate in the enteric nervous system and then spread in a prion-like fashion to the brain. The reported close relation between the prevalence of Parkinson’s disease and the dysbiosis supports this idea. Of note is that the pathological processes start years before the clinical onset of the disease; therefore, targeting gut microbiota seems to be an attractive approach to neuroprotection against Parkinson’s disease.
In light of the above, diet is a significant factor modulating the initiation and development of the disorder as it influences the microbiota throughout a host’s life. Phytoconstituents demonstrating selective prebiotic and antimicrobial effects play an important role. Particularly significant are high-molecular-weight polyphenols, which can be biotransformed by colonic bacteria into metabolites with greater activity than their natural precursors, exerting beneficial effects on the brain. In this context, urolithins - products of catabolism of ellagitannins, mainly pomegranate’s punicalagins, have recently attracted considerable interest, as they possess anti-inflammatory, antioxidant, antiapoptotic and antiglycative potential. The results of our study support the contribution of urolithin A to the overall neuroprotective effects demonstrated by pomegranate in a rat model of Parkinson’s disease. We have confirmed the presence of the colonic metabolite both in plasma and in the brains of rats treated with pomegranate juice, which correlated well with an improvement in their cognitive and motor functions and a decreased degeneration in the brain.