Yamamoto et al. BMC Genomics 2012, 13:335 http://www.biomedcentral.com/1471-2164/13/335 Page 9 of 15 Figure 8 Signal pathways overrepresented in SI of 0WexGF, 5WexGF and SPF mice compared with GF mice. MGP analysis was performed using signal pathways and chains in the TRANTHPATH database. The pathways/chains were sorted according to the integrated p-value (q) and those with q < 0.001 have been represented. Some pathways/chains were classified by their biological contexts and colored as represented in the figure. profile of chemokine signaling in 5WexGF mice relates to the failure to acquire immune tolerance, it may be ne- cessary to examine chemokine production in epithelial cells isolated from 5WexGF intestines. Our findings col- lectively suggest that the encounter with environmental microbiota during the specific time interval within the neonatal period is critically important for the develop- ment of normal immune system responsiveness to microorganisms, both commensal and infectious. Previous transcriptomics studies focusing on the role of commensal bacteria [43-46] differ from the present study with respect to animal species (mice vs. rats vs. piglets), tissues (epithelium/epithelial cells vs. whole intestines), ages at the time of sampling (pups vs. pu- berty vs. adult), means of manipulation of microbiota (conventionalization vs. monoassociation vs. antibiotic eradication of bacteria), microarray platforms, and statis- tical methodologies. However, the results of these studies are similar to ours in several respects such as prominent alteration of the expression profiles for antigen presenta- tion, xenobiotic systems, and IFN signaling. To shed additional light on the "hygiene hypothesis", a careful