title: Colonic bacterial composition in Parkinson's disease.
abstract: BACKGROUND
  We showed that Parkinson's disease (PD) patients have alpha-synuclein (α-Syn) aggregation in their colon with evidence of colonic inflammation. If PD patients have altered colonic microbiota, dysbiosis might be the mechanism of neuroinflammation that leads to α-Syn misfolding and PD pathology.
  
  
  METHODS
  Sixty-six sigmoid mucosal biopsies and 65 fecal samples were collected from 38 PD patients and 34 healthy controls. Mucosal-associated and feces microbiota compositions were characterized using high-throughput ribosomal RNA gene amplicon sequencing. Data were correlated with clinical measures of PD, and a predictive assessment of microbial community functional potential was used to identify microbial functions.
  
  
  RESULTS
  The mucosal and fecal microbial community of PD patients was significantly different than control subjects, with the fecal samples showing more marked differences than the sigmoid mucosa. At the taxonomic level of genus, putative, "anti-inflammatory" butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia were significantly more abundant in feces of controls than PD patients. Bacteria from the genus Faecalibacterium were significantly more abundant in the mucosa of controls than PD. Putative, "proinflammatory" Proteobacteria of the genus Ralstonia were significantly more abundant in mucosa of PD than controls. Predictive metagenomics indicated that a large number of genes involved in metabolism were significantly lower in the PD fecal microbiome, whereas genes involved in lipopolysaccharide biosynthesis and type III bacterial secretion systems were significantly higher in PD patients.
  
  
  CONCLUSIONS
  This report provides evidence that proinflammatory dysbiosis is present in PD patients and could trigger inflammation-induced misfolding of α-Syn and development of PD pathology.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA.|Department of Pharmacology, Rush University Medical Center, Chicago, Illinois, USA.|Department of Physiology, Rush University Medical Center, Chicago, Illinois, USA.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.affiliation: DNA Services Facility, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA.|Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Green
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Engen
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Voigt
authors.affiliation: DNA Services Facility, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Ankur
authors.initials: A
authors.lastname: Naqib
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA.|Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Forsyth
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Ece
authors.initials: E
authors.lastname: Mutlu
authors.affiliation: Department of Neurology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Shannon
mesh_terms: D000328:Adult; D000368:Aged; D012809:Colon, Sigmoid / Q000382:microbiology*; D064806:Dysbiosis / Q000150:complications*; D005243:Feces / Q000382:microbiology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology*; D017510:Protein Folding; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D051844:alpha-Synuclein
keywords: a-synuclein; colonic mucosa and feces; dysbiosis; microbiota; putative butyrate producing short-chain fatty acids