We found that colonic epithelial cells from pIgR KO mice differentially expressed (more than twofold change) more than 200 genes compared with cells from WT mice, and Mitomycin C cost upregulated the expression of antimicrobial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and WT mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium-induced

colitis, and that this was driven by their conventional intestinal microbiota. Thus, in the absence of pIgR, the stability of the commensal microbiota is disturbed, gut homeostasis is compromised, and the outcome of colitis is significantly worsened. Mucus membranes lining the gastrointestinal tract are constantly bombarded by an enormous number of foreign antigens derived from dietary products HM781-36B cell line and the commensal microbiota. The microbial load of the human colon (about 1014 bacteria) is estimated to be more than ten times the number of eukaryotic cells in the body [1, 2]. The commensal microbiota lives in a mutualistic relationship with their host and provides several benefits. These include the digestion of insoluble fibers and increased energy usage of foods, synthesis of vitamin K [3, 4], and niche occupation that could otherwise

be exploited by pathogens [5]. The aggregate gene pool of the microbiota, a.k.a. the metagenome, contains 150 times more genes than the

human genome [6, 7]. Although the human microbiome varies considerably between hosts, our core microbiome has been classified into only three types of communities termed enterotypes [8]. A first line of immune defense mediated by nonspecific innate immune effector components has evolved to protect the epithelial barrier without causing inflammatory immune responses [9]. The primary effector component of the adaptive immune system at mucosal sites is secretory IgA (SIgA) [10]. These antibodies are generated by cooperation between dimeric IgA (dIgA)-producing plasma cells and mucosal epithelial crotamiton cells (ECs), which actively transport dIgA antibodies to the lumen by polymeric Ig receptor (pIgR)-mediated transfer. During transcytosis, the extracellular domain of the pIgR, known as secretory component, becomes covalently coupled to the IgA molecule and final release of receptor–cargo complex occurs by endoproteolytic cleavage of the pIgR [11]. Normally, 80% of the body’s plasma cells are located in the gut and most of these produce dIgA [10]. Germ-free mice, however, have an immature immune system with a greatly reduced number of IgA-producing plasma cells and T cells in the intestinal lamina propria [4]. Upon colonization of germ-free mice with conventional nonpathogenic intestinal bacteria, both T-cell responses and IgA production is activated in the gut.