title: Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease.
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.
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Sae
authors.initials: S
authors.lastname: Goto
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsuji
authors.affiliation: Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Asahara
authors.affiliation: Yakult Central Institute, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nomoto
authors.affiliation: Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Minato
authors.affiliation: Department of School Health Sciences, Aichi University of Education, Kariya, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kinji
authors.initials: K
authors.lastname: Ohno
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hirayama
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D001419:Bacteria / Q000235:genetics; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D003248:Constipation / Q000097:blood / Q000382:microbiology; D004269:DNA, Bacterial / Q000235:genetics; D064806:Dysbiosis / Q000097:blood* / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D054892:Metagenome / Q000235:genetics; D010300:Parkinson Disease / Q000097:blood* / Q000382:microbiology*; D010539:Permeability; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D008562:Membrane Glycoproteins; D012336:RNA, Ribosomal, 16S; D000099231:Lipopolysaccharide-Binding Protein