Intestinal Inflammation and Parkinson's Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease which significantly influences the life quality of patients. The protein α-synuclein plays an important driving role in PD occurrence and development. Braak's hypothesis suggests that α-synuclein is produced in intestine, and then spreads into the central nervous system through the vagus nerve. The abnormal expression of α-synuclein has been found in inflammatory bowel disease (IBD). Intestinal inflammation and intestinal dysbiosis have been involved in the occurrence and development of PD. The present review aimed to summarize recent advancements in studies focusing on intestinal inflammation and PD, especially the mechanisms through which link intestinal inflammation and PD. The intestinal dysfunctions such as constipation have been introduced as non-motor manifestations of PD. The possible linkages between IBD and PD, including genetic overlaps, inflammatory responses, intestinal permeability, and intestinal dysbiosis, are mainly discussed. Although it is not confirmed whether PD starts from intestine, intestinal dysfunction may affect intestinal microenvironment to influence central nervous system, including the α-synuclein pathologies and systematic inflammation. It is expected to develop some new strategies in the diagnosis and treatment of PD from the aspect of intestine. It may also become an exciting direction to find better ways to regulate the composition of gut microorganism to treat PD.

Keywords: Inflammation; Parkinson’s disease; inflammatory bowel disease; microbiota.

Figure 1.

Intestinal dysfunctions in PD. Intestinal dysfunctions occurring in PD are marked in bubbles. The color level of the bubbles represents the OR of intestinal dysfunctions in PD. IBD, inflammatory bowel disease; IBS, irritable bowel syndrome, IETM: intestinal endotoxemia, H. pylori: Helicobacter pylori, OR: odd ratio.

Figure 2.

Potential linkage relationship between IBD and PD. BBB, blood-brain barrier; SCFA, short chain fatty acid.

Figure 3.

Intestinal dysbiosis in IBD contribute to PD. A refers to Revotellaceae and Ruminoccous; B refers to Roseburia; C, refers to Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus and Blautia. D, E and F respectively refers to Prevotella, Lactobacillus and Prevotellaceae. ENS, enteric nervous system; LPS, lipopolysaccharide; TLR4, Toll-like receptor 4; TJs, tight junctions; ROS, reactive oxygen species; H2S, hydrogen sulfide; SCFAs, short chain fatty acids.