title: Fecal Microbiota in Pediatric Inflammatory Bowel Disease and Its Relation to Inflammation.
abstract: OBJECTIVE
  Inflammatory bowel disease (IBD) is considered to result from interplay between host and intestinal microbiota. While IBD in adults has shown to be associated with marked changes in the intestinal microbiota, there are only a few studies in children, and particularly studies focusing on therapeutic responses are lacking. Hence, this prospective study addressed the intestinal microbiota in pediatric IBD especially related to the level of inflammation.
  
  
  METHODS
  In total, 68 pediatric patients with IBD and 26 controls provided stool and blood samples in a tertiary care hospital and 32 received anti-tumor necrosis factor-α (anti-TNF-α). Blood inflammatory markers and fecal calprotectin levels were determined. The intestinal microbiota was characterized by phylogenetic microarray and qPCR analysis.
  
  
  RESULTS
  The microbiota varied along a gradient of increasing intestinal inflammation (indicated by calprotectin levels), which was associated with reduced microbial richness, abundance of butyrate producers, and relative abundance of Gram-positive bacteria (especially Clostridium clusters IV and XIVa). A significant association between microbiota composition and inflammation was indicated by a set of bacterial groups predicting the calprotectin levels (area under curve (AUC) of 0.85). During the induction of anti-TNF-α, the microbial diversity and similarity to the microbiota of controls increased in the responder group by week 6, but not in the non-responders (P<0.01; response related to calprotectin levels). The abundance of six groups of bacteria including those related to Eubacterium rectale and Bifidobacterium spp. predicted the response to anti-TNF-α medication.
  
  
  CONCLUSIONS
  Intestinal microbiota represents a potential biomarker for correlating the level of inflammation and therapeutic responses to be further validated.
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
authors.affiliation: Immunobiology Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Korpela
authors.affiliation: Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Tytti
authors.initials: T
authors.lastname: Jaakkola
authors.affiliation: Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Madharasi V A
authors.initials: MV
authors.lastname: Pichai
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Zoetendal
authors.affiliation: Immunobiology Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Salonen
authors.affiliation: 1] Immunobiology Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland [2] Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands [3] Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001441:Bacteroides fragilis / Q000235:genetics / Q000302:isolation & purification; D001644:Bifidobacterium / Q000235:genetics / Q000302:isolation & purification; D016022:Case-Control Studies; D002648:Child; D003013:Clostridium / Q000235:genetics / Q000302:isolation & purification; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*; D005051:Eubacterium / Q000235:genetics / Q000302:isolation & purification; D005243:Feces / Q000737:chemistry / Q000382:microbiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D064307:Microbiota / Q000235:genetics*; D058889:Molecular Typing; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D039841:Leukocyte L1 Antigen Complex; D014409:Tumor Necrosis Factor-alpha