Abstract

Because germ-free animals are difficult to generate and maintain, antibiotic-treated animals are often substituted in studies designed to determine the role of the normal microflora in health and disease. To determine the extent to which antibiotic (AB) treatment mimics the germ-free condition, and to ascertain the direct effects of AB on the host, we orally treated conventional and germ-free (GF) mice with a combination of four antibiotics for one month and performed microarray analysis of terminal ileum. We observed a decrease in the expression of T lymphocyte genes in both AB-treated and GF mice whereas B-lymphocyte transcripts had much higher expression in AB-treated and conventional than in GF mice. This result was confirmed at the cell number level in the tissue. Among the direct effects of antibiotics independent on flora, we found a decrease in the expression of genes related to mitochondrial functions and cell division. Concordantly, we detected lower amounts of mitochondria and a higher rate of cell death in the gut epithelial cells of AB-treated than of control mice. In conclusion, we found that antibiotics treatment only partially recapitulates the GF condition for mucosal immune system being able to mimic the germ-free status of mucosal T lymphocytes but not of B lymphocytes. In addition, antibiotics have some major direct effects decreasing energy metabolism in the host tissue independently on flora elimination.

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