An oral introduction of intestinal bacteria prevents the development of a long-term Th2-skewed immunological memory induced by neonatal antibiotic treatment in mice

BACKGROUND: Recent epidemiological studies indicate that antibiotic use in infancy may be associated with an increased risk of developing atopy. Our previous work on animals demonstrated that kanamycin use during infancy promotes a shift in the Th1/Th2 balance towards a Th2-dominant immunity. OBJECTIVE: The first purpose of this study is to clarify whether or not the supplementation of intestinal bacteria can reverse such a Th2-skewed response induced by neonatal antibiotic use. The second objective is to elucidate the contribution of genetic factors to antibiotic-induced immune-deviation. METHODS: BALB/c or C57BL/6 mice at 3 weeks of age were orally administered 600 microg/day of kanamycin sulphate for seven consecutive days. Thereafter, the mice were inoculated with one type of intestinal bacterial species: Enterococcus faecalis, Lactobacillus acidophilus or Bacteroides vulgatus. Blood samples were collected 10 weeks after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on Th1/Th2 balance was evaluated based on in vivo antibody levels. RESULTS: A kanamycin-induced elevation of the serum IgE levels was reversed by the supplementation with Enterococcus faecalis, and to a lesser extent by that with Lactobacillus acidophilus. The IgE/IgG2a ratio in the mice supplemented with Enterococcus faecalis significantly decreased in comparison with that in the kanamycin-treated mice without any bacterial supplementation, while such a ratio was enhanced in the mice inoculated with Bacteroides vulgatus. No antibiotic-induced Th2-skewed response was seen in C57BL/6 mice that are genetically biased towards Th1-dominant immunity. CONCLUSION: These results suggest that adequate probiotic intervention after antibiotic treatment may improve the intestinal ecosystem, and thereby prevent the Th2-shifted immunity induced by neonatal antibiotic use. In addition, the difference of genetic backgrounds also contributes to such an antibiotic-induced Th2-skewed response.