期刊
JOURNAL OF PARKINSONS DISEASE
卷 7, 期 2, 页码 331-346出版社
IOS PRESS
DOI: 10.3233/JPD-160991
关键词
Multiple system atrophy; microbiota; colonic mucosa and feces; lipopolysaccharide; Zonula Occludens-1; Toll-like-receptor-4
资金
- Parkinson Disease Foundation
- Michael J. Fox Foundation
Background: Recent evidence suggests that Parkinson's disease (PD) is associated with intestinal microbiota dysbiosis, abnormal intestinal permeability, and intestinal inflammation. Objective: Our study aimed to determine if these gut abnormalities are present in another synucleinopathy, multiple system atrophy (MSA). Methods: In six MSA and 11 healthy control subjects, we performed immunohistochemistry studies of colonic sigmoid mucosa to evaluate the intestinal barrier marker Zonula Occludens-1 and the endotoxin-related inflammation marker Toll-likereceptor- 4 expression. We also assessed colonic sigmoid mucosal and fecal microbiota compositions using high-throughput 16S ribosomal RNA gene amplicon sequencing. Results: MSA subjects showed disrupted tight junction protein Zonula Occludens-1 structure in sigmoid mucosa tissue suggesting intestinal barrier dysfunction. The lipopolysaccharide specific inflammatory receptor Toll-like-receptor-4 was significantly higher in the colonic sigmoid mucosa in MSA relative to healthy controls. Microbiota analysis suggested high relative abundance of gram-negative, putative pro-inflammatory bacteria in various family and genus level taxa, from the phylum Bacteroidetes and Proteobacteria, in MSA feces and mucosa. At the taxonomic level of genus, putative antiinflammatory butyrate-producing bacteria were less abundant in MSA feces. Predictive functional analysis indicated that the relative abundance of a number of genes involved in metabolism were lower inMSAfeces, whereas the relative abundance of genes involved in lipopolysaccharide biosynthesis were higher in bothMSAfeces and mucosa compared to healthy controls. Conclusions: This proof-of-concept study provides preliminary evidence that like PD, MSA subjects display evidence of disrupted intestinal barrier integrity, increased marker of endotoxin-related intestinal inflammation, and pro-inflammatory colonic microbiota.
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