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Antibiotic Administration Early in Life Impairs Specific Humoral Responses to an Oral Antigen and Increases Intestinal Mast Cell Numbers and Mediator Concentrations

S. Nutten,^* A. Schumann, D. Donnicola, A. Mercenier, S. Rami, and C. L. Garcia-Rodenas

Nestlé Research Center, Lausanne, Switzerland

Received 13 February 2006/ Returned for modification 31 March 2006/ Accepted 11 November 2006

In this study, we assessed the effect of administering the antibiotic amoxicillin to rat pups on the immune response to orally fed ovalbumin (OVA). We first established that amoxicillin administration durably altered the gut microbiota of these animals. In parallel, we observed that the induction of the specific humoral response to ovalbumin was impaired when it occurred during antibiotic administration to the rat pups. We also examined the consequences of those observations on further allergic reactions. Amoxicillin administration had no significant impact on subsequent sensitization to OVA, as nonexacerbated systemic allergic responses were induced in antibiotic-treated animals. However, increased rat mast cell protease II levels and higher mast cell numbers were detected in their small intestines, independently of the antigen administration. Globally, our data suggest that antibiotic administration early in life negatively affects the specific immune response to a luminal antigen when it is first introduced during antibiotic administration. The increased mast cell numbers and mediator concentrations in the intestinal mucosae of the antibiotic-treated animals may testify to the early stages of an altered immune system homeostasis.

Published ahead of print on 6 December 2006.

These authors contributed equally to the work presented in this report.