title: Host-microbe relationships in inflammatory bowel disease detected by bacterial and metaproteomic analysis of the mucosal-luminal interface.
abstract: BACKGROUND
  Host-microbe interactions at the intestinal mucosal-luminal interface (MLI) are critical factors in the biology of inflammatory bowel disease (IBD).
  
  
  METHODS
  To address this issue, we performed a series of investigations integrating analysis of the bacteria and metaproteome at the MLI of Crohn's disease, ulcerative colitis, and healthy human subjects. After quantifying these variables in mucosal specimens from a first sample set, we searched for bacteria exhibiting strong correlations with host proteins. This assessment identified a small subset of bacterial phylotypes possessing this host interaction property. Using a second and independent sample set, we tested the association of disease state with levels of these 14 "host interaction" bacterial phylotypes.
  
  
  RESULTS
  A high frequency of these bacteria (35%) significantly differentiated human subjects by disease type. Analysis of the MLI metaproteomes also yielded disease classification with exceptional confidence levels. Examination of the relationships between the bacteria and proteins, using regularized canonical correlation analysis (RCCA), sorted most subjects by disease type, supporting the concept that host-microbe interactions are involved in the biology underlying IBD. Moreover, this correlation analysis identified bacteria and proteins that were undetected by standard means-based methods such as analysis of variance, and identified associations of specific bacterial phylotypes with particular protein features of the innate immune response, some of which have been documented in model systems.
  
  
  CONCLUSIONS
  These findings suggest that computational mining of mucosa-associated bacteria for host interaction provides an unsupervised strategy to uncover networks of bacterial taxa and host processes relevant to normal and disease states. (Inflamm Bowel Dis 2012;).
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, CA 90095, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Presley
authors.forename: Jingxiao
authors.initials: J
authors.lastname: Ye
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Leblanc
authors.forename: Zhanpan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ruegger
authors.forename: Jeff
authors.initials: J
authors.lastname: Allard
authors.forename: Dermot
authors.initials: D
authors.lastname: McGovern
authors.forename: Andrew
authors.initials: A
authors.lastname: Ippoliti
authors.forename: Bennett
authors.initials: B
authors.lastname: Roth
authors.forename: Xinping
authors.initials: X
authors.lastname: Cui
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Jeske
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.forename: James
authors.initials: J
authors.lastname: Borneman
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D002432:Cecum / Q000378:metabolism / Q000382:microbiology; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000382:microbiology*; D012809:Colon, Sigmoid / Q000378:metabolism / Q000382:microbiology; D003424:Crohn Disease / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D012329:RNA, Bacterial / Q000032:analysis*; D012335:RNA, Ribosomal / Q000032:analysis*
chemical_list: D011506:Proteins; D012329:RNA, Bacterial; D012335:RNA, Ribosomal