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1 Nutrition and Health, Nestle Research Center, Lausanne 26, Switzerland; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
2 Nutrition and Health, Nestle Research Center, Lausanne 26, Switzerland
3 Bioanalytical Science, Nestle Research Center, Lausanne 26, Switzerland
* To whom correspondence should be addressed. E-mail: clara.garcia{at}rdls.nestle.com.
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. In order 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) till d17 or d21. Luminal microbiota composition and global gene expression profile were analysed 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 down-regulated by the Clamoxyl® treatment. A significant down-regulation of MHC class Ib and II genes, involved in antigen presentation, was also observed. Conversely, mast cell protease expression was up-regulated. 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.
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