Alistic relationship between bacteria and host has developed. The intestinal microflora influences the host in different ways by modulating the immune system, protecting against pathogen invasion and attachment, and contributing to digestion and nutritional uptake [3]. In a healthy gut the synergistic co-existence of intestinal microflora and the host is secured by an intact mucosal barrier. The barrier is provided by the intestinal epithelium, consisting of absorptive, goblet, Paneth and neuroendocrine cells, separating the intestinal wall from the luminal microbes. Goblet cells secretemucins, e.g. Muc1 and Muc2 as structural proteins of the protective mucus layer covering the whole gastrointestinal tract [4]. Moreover, epithelial cells produce broad-spectrum antimicrobial peptides, including defensins [5?]. Once secreted, the small cationic defensins are fixed in the negatively charged mucus [9]. This mucus barrier is the first front of gut defence shielding the intestinal wall from luminal microbiota. The intestinal epithelium differentiates from multipotent stem cells located at the 18325633 bottom of the crypt and undergoes a rapid and continuous regeneration [10]. This process is regulated by a complex network of different differentiation signals. For example, the early determination of secretory versus absorptive cells is regulated by antagonistic interplay of the Notch target gene Hes1 and the basic helix oop elix transcription MedChemExpress SPI 1005 factor Hath1. In progenitor cells expressing Hes1, Hath1 gene expression is blocked, directing the cells to the absorptive fate. In contrast, inBacteria Regulate Intestinal DifferentiationTable 1. Characteristics of the bacterial strains.Strain E. coli Nissle 1917 (DSM 6601) EcNDfliA EcNDfliC EcNDflgE EcNDfim EcNDfoc EcNDcsgBA E. coli K-12 L. fermentum L. acidophilus B. longum (DSM 20219T) B. breve B. adolescentis TSD B. vulgatus E. coli DSM 17252 S2 G1: E. coli Genotype 1/2 S2 G2: E. coli Genotype 3/10 S2 G3: E. coli Genotype 4/Stereotype O6:K5:HCharacteristics/Isolatetypes/Deletions* Apathogen, pharmaceutical strain Sigma factor of flagella genes* flagellin* hook* Type 1 pili* F1C pili* Curli-negative*Source ACS ?WURDSM 498 PZ 1162 PZ 1138 PZ 1323 Ha6/14c PZ 4009 DSMReference strain Intestinal isolate Industrial probiotic strain Intestinal isolate Intestinal isolate Intestinal isolate Intestinal isolateDSMZ ACS ACS (GR) ACS ACS ACS DSMZ SYMOsp.:H-Probiotic strainO 13.:H-Probiotic strainOsp.:H-Probiotic strainEcN…E. coli Nissle 1917. ACS: Ardeypharm collection of strains, Pharma-Zentrale GmbH, Herdecke, Germany. ??WUR: Collection of strains, University of Wurzburg. DSMZ: German Collection of Microorganisms and Cell cultures, Braunschweig, Germany. GR: Strain collection of G. Reuter (strain deposited by Mitusoka at the Japanese Collection of Microorganisms). SYM: SymbioPharm GmbH, Germany. doi:10.1371/journal.pone.0055620.tprogenitors with inactive Notch/Hes1 signaling, the Hath1 gene can be transcriptionally order AKT inhibitor 2 activated and these cells transit to the secretory lineage [11,12]. The predetermined cells of the secretory line require additional signals for differentiation to specific cell types such as, for goblet cells, the zinc-finger transcription factor KLF4 [13]. Dysregulation of this regulatory network may lead to defective epithelial differentiation and finally to altered function of the mucosal barrier as shown in both forms of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC.Alistic relationship between bacteria and host has developed. The intestinal microflora influences the host in different ways by modulating the immune system, protecting against pathogen invasion and attachment, and contributing to digestion and nutritional uptake [3]. In a healthy gut the synergistic co-existence of intestinal microflora and the host is secured by an intact mucosal barrier. The barrier is provided by the intestinal epithelium, consisting of absorptive, goblet, Paneth and neuroendocrine cells, separating the intestinal wall from the luminal microbes. Goblet cells secretemucins, e.g. Muc1 and Muc2 as structural proteins of the protective mucus layer covering the whole gastrointestinal tract [4]. Moreover, epithelial cells produce broad-spectrum antimicrobial peptides, including defensins [5?]. Once secreted, the small cationic defensins are fixed in the negatively charged mucus [9]. This mucus barrier is the first front of gut defence shielding the intestinal wall from luminal microbiota. The intestinal epithelium differentiates from multipotent stem cells located at the 18325633 bottom of the crypt and undergoes a rapid and continuous regeneration [10]. This process is regulated by a complex network of different differentiation signals. For example, the early determination of secretory versus absorptive cells is regulated by antagonistic interplay of the Notch target gene Hes1 and the basic helix oop elix transcription factor Hath1. In progenitor cells expressing Hes1, Hath1 gene expression is blocked, directing the cells to the absorptive fate. In contrast, inBacteria Regulate Intestinal DifferentiationTable 1. Characteristics of the bacterial strains.Strain E. coli Nissle 1917 (DSM 6601) EcNDfliA EcNDfliC EcNDflgE EcNDfim EcNDfoc EcNDcsgBA E. coli K-12 L. fermentum L. acidophilus B. longum (DSM 20219T) B. breve B. adolescentis TSD B. vulgatus E. coli DSM 17252 S2 G1: E. coli Genotype 1/2 S2 G2: E. coli Genotype 3/10 S2 G3: E. coli Genotype 4/Stereotype O6:K5:HCharacteristics/Isolatetypes/Deletions* Apathogen, pharmaceutical strain Sigma factor of flagella genes* flagellin* hook* Type 1 pili* F1C pili* Curli-negative*Source ACS ?WURDSM 498 PZ 1162 PZ 1138 PZ 1323 Ha6/14c PZ 4009 DSMReference strain Intestinal isolate Industrial probiotic strain Intestinal isolate Intestinal isolate Intestinal isolate Intestinal isolateDSMZ ACS ACS (GR) ACS ACS ACS DSMZ SYMOsp.:H-Probiotic strainO 13.:H-Probiotic strainOsp.:H-Probiotic strainEcN…E. coli Nissle 1917. ACS: Ardeypharm collection of strains, Pharma-Zentrale GmbH, Herdecke, Germany. ??WUR: Collection of strains, University of Wurzburg. DSMZ: German Collection of Microorganisms and Cell cultures, Braunschweig, Germany. GR: Strain collection of G. Reuter (strain deposited by Mitusoka at the Japanese Collection of Microorganisms). SYM: SymbioPharm GmbH, Germany. doi:10.1371/journal.pone.0055620.tprogenitors with inactive Notch/Hes1 signaling, the Hath1 gene can be transcriptionally activated and these cells transit to the secretory lineage [11,12]. The predetermined cells of the secretory line require additional signals for differentiation to specific cell types such as, for goblet cells, the zinc-finger transcription factor KLF4 [13]. Dysregulation of this regulatory network may lead to defective epithelial differentiation and finally to altered function of the mucosal barrier as shown in both forms of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC.
