Fecal Microbiota in Pediatric Inflammatory Bowel Disease and Its Relation to Inflammation

Am J Gastroenterol. 2015 Jun;110(6):921-30. doi: 10.1038/ajg.2015.149. Epub 2015 May 19.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents / therapeutic use
  • Bacteroides fragilis / genetics
  • Bacteroides fragilis / isolation & purification
  • Bifidobacterium / genetics
  • Bifidobacterium / isolation & purification
  • Case-Control Studies
  • Child
  • Clostridium / genetics
  • Clostridium / isolation & purification
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / microbiology*
  • Crohn Disease / drug therapy
  • Crohn Disease / metabolism
  • Crohn Disease / microbiology*
  • Eubacterium / genetics
  • Eubacterium / isolation & purification
  • Feces / chemistry
  • Feces / microbiology*
  • Female
  • Humans
  • Inflammation / metabolism
  • Leukocyte L1 Antigen Complex / metabolism
  • Male
  • Microbiota / genetics*
  • Molecular Typing
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • Leukocyte L1 Antigen Complex
  • Tumor Necrosis Factor-alpha

Supplementary concepts

  • Pediatric Crohn's disease
  • Pediatric ulcerative colitis