Role of the Gut-Brain Axis, Gut Microbial Composition, Diet, and Probiotic Intervention in Parkinson's Disease

Abstract

Parkinson's disease (PD) is the second-most prevalent neurodegenerative or neuropsychiatric disease, affecting 1% of seniors worldwide. The gut microbiota (GM) is one of the key access controls for most diseases and disorders. Disturbance in the GM creates an imbalance in the function and circulation of metabolites, resulting in unhealthy conditions. Any dysbiosis could affect the function of the gut, consequently disturbing the equilibrium in the intestine, and provoking pro-inflammatory conditions in the gut lumen, which send signals to the central nervous system (CNS) through the vagus enteric nervous system, possibly disturbing the blood-brain barrier. The neuroinflammatory conditions in the brain cause accumulation of α-syn, and progressively develop PD. An important aspect of understanding and treating the disease is access to broad knowledge about the influence of dietary supplements on GM. Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotic supplementation improves the function of the CNS, and improves the motor and non-motor symptoms of PD. Probiotic supplementation could be an adjuvant therapeutic method to manage PD. This review summarizes the role of GM in health, the GM-brain axis, the pathogenesis of PD, the role of GM and diet in PD, and the influence of probiotic supplementation on PD. The study encourages further detailed clinical trials in PD patients with probiotics, which aids in determining the involvement of GM, intestinal mediators, and neurological mediators in the treatment or management of PD.

Keywords: Parkinson’s disease; central nervous system; gut microbiota; gut–brain axis; inflammation; neurodegenerative diseases; probiotics.

Figure 1

(a) Diagrammatic representation of predominant gut microbiome members in humans across ages. A: newborn baby; B: pre-term infants; C: infant from vaginal birth; D: infant from caesarean; E: breastfeeding baby; F: formula-feeding baby; G: children; H: adult; I: Elders; J: centenarians; K: semi-supercentenarians. (b) The altered gut microbiome in Parkinson’s disease. ↑ indicates the increase in the abundance of microbes; ↓ indicates the decrease in the abundance of microbes.

Figure 2

Bidirectional communication and the mediators of the gut–brain axis.

Figure 3

The gut dysbiosis and Parkinson’s disease. Gut dysbiosis and defects in intestinal barrier function facilitate the release of material metabolites, endotoxins, and other antigens into the gastrointestinal system, which further activates the immune system and the release of pro-inflammatory cytokines. Chronic immune activation may cause neuroinflammation and neurodegenerative diseases (Figure created using BioRender.com).

Figure 4

The representation of molecular signaling and progression of Parkinson’s disease in substantia nigra. Gut dysbiosis activates the immune system. The released cytokines may disturb the blood–brain barrier, facilitating the entry of bacterial metabolites and other antigens to the central nervous system. It causes α-syn aggregation in the substantia nigra of the brain. Hyperphosphorylated α-syn recruits the TLR4 and CD14+ in the microglial cells, promoting the neuronal immune responses by activating the NF-κb, pro-IL β pro-inflammatory cytokines. The exact mechanism and the players are not elucidated completely (Figure created using BioRender.com).

Figure 5

Schematic illustration of endocrine, immune, and neuroimmune signaling pathways. Gut microbes help maintain intestinal integrity by balancing the microbial products, neurotransmitters, and SCFAs across the enteric and immune systems. Microbial dysbiosis triggers activated immune cells, macrophages, dendritic cells, and pro-inflammatory cytokines. (Figure created using BioRender.com).