Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease

PLoS One. 2015 Nov 5;10(11):e0142164. doi: 10.1371/journal.pone.0142164. eCollection 2015.

Abstract

Background: The intestine is one of the first affected organs in Parkinson's disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon.

Methods: We recruited 52 PD patients and 36 healthy cohabitants. We measured serum markers and quantified the numbers of 19 fecal bacterial groups/genera/species by quantitative RT-PCR of 16S or 23S rRNA. Although the six most predominant bacterial groups/genera/species covered on average 71.3% of total intestinal bacteria, our analysis was not comprehensive compared to metagenome analysis or 16S rRNA amplicon sequencing.

Results: In PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasseri subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD.

Conclusions: The permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Aged
  • Bacteria / genetics
  • Carrier Proteins / blood*
  • Case-Control Studies
  • Constipation / blood
  • Constipation / microbiology
  • DNA, Bacterial / genetics
  • Dysbiosis / blood*
  • Dysbiosis / microbiology*
  • Feces / microbiology
  • Female
  • Humans
  • Intestinal Mucosa / microbiology*
  • Male
  • Membrane Glycoproteins / blood*
  • Metagenome / genetics
  • Parkinson Disease / blood*
  • Parkinson Disease / microbiology*
  • Permeability
  • RNA, Ribosomal, 16S / genetics

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • DNA, Bacterial
  • Membrane Glycoproteins
  • RNA, Ribosomal, 16S
  • lipopolysaccharide-binding protein

Grant support

The study was supported by Grants-in-Aid from the MEXT and MHLW of Japan, as well as Yakult Central Institute. The funders did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder Yakult Central Institute provided support in the form of salaries for authors [HT, TA, and KN], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.