Histamine-2 receptor blockers alter the fecal microbiota in premature infants

J Pediatr Gastroenterol Nutr. 2013 Apr;56(4):397-400. doi: 10.1097/MPG.0b013e318282a8c2.


Objectives: Bacterial colonization is considered a major risk factor for necrotizing enterocolitis (NEC). The objective of the present study was to test the hypothesis that histamine-2 receptor (H2-) blockers alter colonic bacterial colonization by analyzing and comparing the fecal microbiota in premature infants with and without H2-blocker therapy using sensitive molecular biological techniques.

Methods: Seventy-six premature infants ≤1500 g or <34 weeks gestation were enrolled in this case-controlled, cross-sectional study. Stool samples were collected from 25 infants receiving H2-blockers and 51 babies who had never received them. Following DNA extraction and PCR amplification of 16S rRNA, 454 pyrosequencing was undertaken and the resulting sequences were subjected to comparison with published sequence libraries.

Results: Proteobacteria and Firmicutes were the major phyla contributing to fecal microbial communities. Microbial diversity was lower, relative abundance of Proteobacteria (primarily of the family Enterobacteriaceae) was increased, whereas that of Firmicutes was decreased in the stools of infants receiving H2-blockers compared with those who had never received them.

Conclusions: Although not designed to look specifically at the effect of H2-blockers on the incidence of NEC, our study suggests that their use lowers fecal microbial diversity and shifts the microfloral pattern toward Proteobacteria. These alterations in fecal microbiota may predispose the vulnerable immature gut to necrotizing enterocolitis and suggest prudence in the use of H2-blockers in the premature infant.

Publication types

  • Multicenter Study

MeSH terms

  • Case-Control Studies
  • Child Development
  • Cross-Sectional Studies
  • Enterocolitis, Necrotizing / epidemiology
  • Enterocolitis, Necrotizing / microbiology
  • Enterocolitis, Necrotizing / prevention & control
  • Feces / microbiology*
  • Female
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / growth & development
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / growth & development
  • Gram-Positive Bacteria / isolation & purification
  • Histamine H2 Antagonists / adverse effects
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / epidemiology
  • Infant, Premature, Diseases / microbiology
  • Infant, Premature, Diseases / prevention & control
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / growth & development
  • Intestinal Mucosa / microbiology
  • Intestines / drug effects*
  • Intestines / growth & development
  • Intestines / microbiology
  • Longitudinal Studies
  • Louisiana / epidemiology
  • Male
  • Proteobacteria / drug effects
  • Proteobacteria / growth & development
  • Proteobacteria / isolation & purification
  • Risk Factors


  • Histamine H2 Antagonists