Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model.
OBJECTIVE
It is known that postnatal functional maturation of the small intestine is facilitated by microbial colonization of the gut. Preterm infants exhibit defects in gut maturation, weak innate immunity against intestinal infection and increased susceptibility to inflammatory disorders, all of which may be related to the inappropriate microbial colonization of their immature intestines. The earliest microbes to colonize the preterm infant gut encounter a naïve, immature intestine. Thus this earliest microbiota potentially has the greatest opportunity to fundamentally influence intestinal development and immune function. The aim of this study was to characterize the effect of early microbial colonization on global gene expression in the distal small intestine during postnatal gut development.


METHODS
Gnotobiotic mouse models with experimental colonization by early (prior to two weeks of life) intestinal microbiota from preterm human infants were utilized. Microarray analysis was used to assess global gene expression in the intestinal epithelium.


CONCLUSIONS
Multiple intestinal genes involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication, and immune function are developmental- and intestinal microbiota- regulated. Using a humanized gnotobiotic mouse model, we demonstrate that certain early preterm infant microbiota from prior to 2 weeks of life specifically induce increased NF-κB activation and a phenotype of increased inflammation whereas other preterm microbiota specifically induce decreased NF-κB activation. These fundamental differences correlate with altered clinical outcomes and suggest the existence of optimal early microbial communities to improve health outcomes.
Department of Pediatrics/Neonatology, University of Chicago, Chicago Illinois, United States of America.
Lei
L
Lu
Department of Pediatrics/Neonatology, University of Chicago, Chicago Illinois, United States of America.
Yueyue
Y
Yu
Department of Pediatrics/Neonatology, University of Chicago, Chicago Illinois, United States of America.
Yuee
Y
Guo
Internal Medicine Residency Program at Reno, University of Nevada School of Medicine, Reno Nevada, United States of America.
Yunwei
Y
Wang
Department of Medicine/Gastroenterology, University of Chicago, Chicago Illinois, United States of America.
Eugene B
EB
Chang
Department of Pediatrics/Neonatology, University of Chicago, Chicago Illinois, United States of America; Department of Medicine/Gastroenterology, University of Chicago, Chicago Illinois, United States of America.
Erika C
EC
Claud
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005856:Germ-Free Life; D006801:Humans; D007234:Infant, Premature; D007249:Inflammation / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy
D016328:NF-kappa B