title: Fecal protease activity is associated with compositional alterations in the intestinal microbiota.
abstract: OBJECTIVE
  Intestinal proteases carry out a variety of functions in the gastrointestinal (GI) tract. Studies have reported that elevated enteric proteases in patients with GI disease can alter intestinal physiology, however the origin (human vs. microbial) of elevated proteases in patients with GI disease is unclear.
  
  
  OBJECTIVE
  The aim of this study was to investigate the association between protease activity and the microbiota in human fecal samples.
  
  
  METHODS
  In order to capture a wide range of fecal protease (FP) activity stool samples were collected from 30 IBS patients and 24 healthy controls. The intestinal microbiota was characterized using 454 high throughput pyro-sequencing of the 16S rRNA gene. The composition and diversity of microbial communities were determined and compared using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline. FP activity levels were determined using an ELISA-based method. FP activity was ranked and top and bottom quartiles (n=13 per quartile) were identified as having high and low FP activity, respectively.
  
  
  RESULTS
  The overall diversity of the intestinal microbiota displayed significant clustering separation (p = 0.001) between samples with high vs. low FP activity. The Lactobacillales, Lachnospiraceae, and Streptococcaceae groups were positively associated with FP activity across the entire study population, whilst the Ruminococcaceae family and an unclassified Coriobacteriales family were negatively associated with FP activity.
  
  
  CONCLUSIONS
  These data demonstrate significant associations between specific intestinal bacterial groups and fecal protease activity and provide a basis for further causative studies investigating the role of enteric microbes and GI diseases.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carroll
authors.forename: Tamar
authors.initials: T
authors.lastname: Ringel-Kulka
authors.forename: Laurent
authors.initials: L
authors.lastname: Ferrier
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.forename: Jennica P
authors.initials: JP
authors.lastname: Siddle
authors.forename: Lionel
authors.initials: L
authors.lastname: Bueno
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Ringel
mesh_terms: D000328:Adult; D004269:DNA, Bacterial / Q000235:genetics; D005243:Feces / Q000201:enzymology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D056546:Lactobacillales / Q000235:genetics / Q000502:physiology; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013289:Streptococcaceae / Q000235:genetics / Q000502:physiology
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D010447:Peptide Hydrolases