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Physiol. Genomics 23: 235-245, 2005. First published August 30, 2005; doi:10.1152/physiolgenomics.00057.2005
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Received 4 March 2005; accepted in final form 23 August 2005.
Physiological Genomics 23:235-245 (2005)
American Physiological Society © 2005 American Physiological Society

Article

Neonatal antibiotic treatment alters gastrointestinal tract developmental gene expression and intestinal barrier transcriptome

Alexandra Schumann1,3, Sophie Nutten1, Dominique Donnicola1, Elena M. Comelli1, Robert Mansourian2, Christine Cherbut1, Irène Corthesy-Theulaz1 and Clara Garcia-Rodenas1

Departments of 1 Nutrition and Health and 2 Bioanalytical Science, Nestle Research Center, Vers-chez-les-Blanc, Lausanne; and 3 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

ABSTRACT

The postnatal maturation of the gut, partially modulated by bacterial colonization, ends up in the establishment of an efficient barrier to luminal antigens and bacteria. The use of broad-spectrum antibiotics in pediatric practices alters the gut bacterial colonization and, consequently, may impair the maturation of the gut barrier function. To test this hypothesis, suckling Sprague-Dawley rats received a daily intragastric gavage of antibiotic (Clamoxyl; an amoxicillin-based commercial preparation) or saline solution from postnatal day 7 (d7) until d17 or d21. Luminal microbiota composition and global gene expression profile were analyzed on samples from small intestine and colon of each group. The treatment with Clamoxyl resulted in the almost-complete eradication of Lactobacillus in the whole intestine and in a drastic reduction of colonic total aerobic and anaerobic bacteria, in particular Enterobacteriacae and Enterococcus. The global gene expression analysis revealed that Clamoxyl affects the maturation process of 249 and 149 Affymetrix probe sets in the proximal and distal small intestine, respectively, and 163 probe sets in the colon. The expression of genes coding for Paneth cell products (defensins, matrilysin, and phospholipase A2) was significantly downregulated by the Clamoxyl treatment. A significant downregulation of major histocompatibility complex (MHC) class Ib and II genes, involved in antigen presentation, was also observed. Conversely, mast cell proteases expression was upregulated. These results suggest that early treatment with a large-spectrum antibiotic deeply affects the gut barrier function at the suckling-weaning interface, a period during which the gut is challenged by an array of novel food-borne antigens.

innate immunity; antigen presentation; mast cell




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