Bifidobacteria are beneficial to human health, but the mechanism remains unknown. We employed oligonucleotide microarrays to identify the Bifidobacterium breve strain Yakult (BbrY) genes up-regulated specifically in mouse intestine. Based on BbrY transcriptional responses in germ-free mice and in fecal cultures, k-means clustering picked up 93 genes that were up-regulated in the mouse intestine and thereafter Venn analysis to exclude genes that were up-regulated in both the mouse intestine and the fecal culture classified 45 genes as up-regulated specifically in the mouse intestine. Most of those genes are involved in sugar transport or sugar liberation, although the functions of several genes are unknown. Most of these genes are clustered on the BbrY genome and appear to be organized into operons. Expressions of several genes were further investigated by real time PCR, revealing that their expression profiles were identical in the mouse cecum and colon. The upregulation of genes involved in sugar liberalization and uptake suggests that BbrY could possibly maintain energy homeostasis inside the mouse intestine, which contains low quantities of readily fermentable sugars. (C) 2011, The Society for Biotechnology, Japan. All rights reserved.