Gastrointestinal system

  • Letter |

    The in vitro generation, from pluripotent stem cells, of three-dimensional human gastric organoids (hGOs) that contain a physiological gastric epithelium comprising both progenitor and differentiated cell types, and have expected functional characteristics is described, as is modelling the pathophysiological response of the human stomach to Helicobacter pylori using these hGOs.

    • Kyle W. McCracken
    • , Emily M. Catá
    •  & James M. Wells
  • Article |

    A framework for metagenomic variation analysis to explore variation in the human microbiome is developed; the study describes SNPs, short indels and structural variants in 252 faecal metagenomes of 207 individuals from Europe and North America.

    • Siegfried Schloissnig
    • , Manimozhiyan Arumugam
    •  & Peer Bork
  • Article |

    The authors have developed a new method, metagenome-wide association study (MGWAS), to compare the combined genetic content of the faecal microbiota of healthy people versus patients with type 2 diabetes; they identify multiple microbial species and metabolic pathways that are associated with either cohort and show that some of these may be used as biomarkers.

    • Junjie Qin
    • , Yingrui Li
    •  & Jun Wang
  • Letter |

    Selective impairment of peripheral regulatory T-cell differentiation is found to result in spontaneous allergic TH2-type inflammation in the intestine and lungs, demonstrating the functional heterogeneity of regulatory T cells generated in the thymus and extrathymically in controlling immune mediated inflammation and disease.

    • Steven Z. Josefowicz
    • , Rachel E. Niec
    •  & Alexander Y. Rudensky
  • Article |

    This paper shows that gut flora can influence cardiovascular disease, by metabolizing a dietary phospholipid. Using a metabolomics approach it is found that plasma levels of three metabolites of dietary phosphatidylcholine—choline, betaine and TMAO—are associated with increased risk of cardiovascular disease in humans. The gut flora is known to have a role in TMAO formation from choline, and this paper shows that dietary choline supplementation enhances macrophage foam cell formation and lesion formation in atherosclerosis-prone mice, but not if the gut flora are depleted with antibiotics.

    • Zeneng Wang
    • , Elizabeth Klipfell
    •  & Stanley L. Hazen
  • Letter |

    This paper shows that the activity of human beta-defensin 1 is regulated by its redox status, with enhanced antibiotic killing activity under reducing conditions as they are found in the distal colon. This is believed to serve to protect the healthy intestinal epithelium against potentially harmful colonization by commensal bacteria and opportunistic fungi. In vitro evidence implicates thioredoxin as the likely reducing agent.

    • Bjoern O. Schroeder
    • , Zhihong Wu
    •  & Jan Wehkamp
  • Letter |

    During periods of fasting the liver produces ketone bodies, which the peripheral tissues can use as a source of energy. Here it is shown that fasting inhibits multi-component mTOR complex 1 (mTORC1) in the liver. Inhibition of mTORC1 is required for activation of PPARα, a master regulator that switches on genes involved in ketogenesis. Livers from aged mice have increased mTORC1 signalling, reduced PPARα activity, and reduced ketone production. The observation that mTORC1 promotes an ageing phenotype in the liver fits well with the observation that inhibition of this pathway increases lifespan in several organisms.

    • Shomit Sengupta
    • , Timothy R. Peterson
    •  & David M. Sabatini
  • Letter |

    These authors describe a molecular pathway by which endothelial cells sustain liver regeneration after surgical resection. Activation of vascular endothelial growth factor-A receptor-2 in a defined subpopulation of liver endothelial cells leads to the upregulation of the endothelial-specific transcription factor Id1, which in turn induces Wnt2 and hepatocyte growth factor, which are secreted from the endothelial cells and trigger hepatocyte proliferation.

    • Bi-Sen Ding
    • , Daniel J. Nolan
    •  & Shahin Rafii
  • Article |

    Salmonella enterica serotype Typhimurium causes acute gut inflammation, which promotes the growth of the pathogen through unknown mechanisms. It is now shown that the reactive oxygen species generated during inflammation react with host-derived sulphur compounds to produce tetrathionate, which the pathogen uses as a terminal electron acceptor to support its growth. The ability to use tetrathionate provides the pathogen with a competitive advantage over bacteria that lack this property.

    • Sebastian E. Winter
    • , Parameth Thiennimitr
    •  & Andreas J. Bäumler
  • Letter |

    Cells that make up the liver are known to be polyploid. These authors show that mouse hepatocytes can increase and decrease their ploidy in vivo; increases occur as a result of failed cytokinesis, and decreases occur as a result of multipolar mitosis. The resulting genetic heterogeneity might be advantageous following hepatic injury, allowing the selection of 'genetically robust' cells from a pre-existing pool of diverse genotypes.

    • Andrew W. Duncan
    • , Matthew H. Taylor
    •  & Markus Grompe
  • Article |

    The microbial content of the human gut has been the focus of much research interest recently. Now another layer of complexity has been added: the viral content of the gut. Virus-like particles were isolated from faecal samples from four sets of identical twins and their mothers, at three time points over a one-year period. The viromes (metagenomes) of these particles were then sequenced. The results show that there is high interpersonal variation in viromes, but that intrapersonal diversity was very low over this time period.

    • Alejandro Reyes
    • , Matthew Haynes
    •  & Jeffrey I. Gordon
  • Letter |

    One of the roles of the human gut microbiota is to break down nutrients using bacterial enzymes that are lacking from the human genome. It is now shown that the gut microbiota of Japanese, but not American, individuals contains porphyranases, enzymes that digest sulphated polysaccharides which are present in the marine environment only. These findings indicate that diet can select for gene content of the human microbiota.

    • Jan-Hendrik Hehemann
    • , Gaëlle Correc
    •  & Gurvan Michel