Altered gut microbiota and intestinal permeability in Parkinson's disease: Pathological highlight to management

摘要

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder, affecting 3.7% of the population over 65 years of age. PD involves degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNPC) with deficiency of dopamine. Genetic factors like SNCA, PARK-2, PARK-7, PINK-1 and LRRK-2 as well as environmental toxins enhance alpha-synuclein, amyloid beta (beta) and tau (tau) proteins aggregation. Moreover, oxidative stress, mitochondria] dysfunctioning, neuroinfiammation, prion like phenomena, excitotoxicity, mutations etc are known to cause pathological insult in PD. Recently, facts indicates strong correlation between gut-brain axis and PD. The communication between the gastrointestinal system (GIT) and central nervous system is bidirectional and it is hypothesized that PD arises in the gut and spreads to brain via vagus nerve that helps to propagate the alpha-synuclein that target brain. The Lewy bodies are found in olfactory bulb, dorsal motor vagal nerve and the ENS of the gut indicate peripheral and central correlation. The alteration of gut microbial flora leads to GIT disturbance which cause neuroinflammation by prion alpha-synuclein expression and produces PD like symptoms. Persistent gut inflammation with spontaneous neuroinflammation is yet need to confirm but increased intestinal permeability and disrupt function of GIT is known to produce non-motor symptoms of PD. The present review is aimed to explore mechanistic approach for gut associated PD symptoms as well as use of probiotics and prebiotics as therapeutic approach to retain gut microbial flora and prevent PD like symptoms.