Gastroenterology

  • Article
    | Open Access

    Human norovirus pathogenesis is incompletely understood due to a lack of appropriate animal disease models. Here, Green et al. show norovirus replication in chromogranin A-positive enteroendocrine cells and other epithelial cells in tissue from a pediatric intestinal transplant recipient with severe gastroenteritis.

    • Kim Y. Green
    • , Stuart S. Kaufman
    • , Bianca M. Nagata
    • , Natthawan Chaimongkol
    • , Daniel Y. Kim
    • , Eric A. Levenson
    • , Christine M. Tin
    • , Allison Behrle Yardley
    • , Jordan A. Johnson
    • , Ana Beatriz F. Barletta
    • , Khalid M. Khan
    • , Nada A. Yazigi
    • , Sukanya Subramanian
    • , Sangeetha R. Moturi
    • , Thomas M. Fishbein
    • , Ian N. Moore
    •  & Stanislav V. Sosnovtsev
  • Article
    | Open Access

    The common ABCG2 variant Q141K contributes to hyperuricemia and gout risk. Here, using a human interventional study and a new orthologous mouse model, the authors report a tissue specific pathobiology of the Q141K variant, and support a significant role for ABCG2 in urate excretion in both the kidney and intestine.

    • Kazi Mirajul Hoque
    • , Eryn E. Dixon
    • , Raychel M. Lewis
    • , Jordyn Allan
    • , Gregory D. Gamble
    • , Amanda J. Phipps-Green
    • , Victoria L. Halperin Kuhns
    • , Anne M. Horne
    • , Lisa K. Stamp
    • , Tony R. Merriman
    • , Nicola Dalbeth
    •  & Owen M. Woodward
  • Article
    | Open Access

    Here the authors perform a gain-of-function screen and identify CDKN2C as a host factor for HBV replication, inducing cell cycle arrest and expression of HBV transcription enhancers. CDKN2C expression correlates with disease progression suggesting a potential role in HBV-induced liver disease.

    • Carla Eller
    • , Laura Heydmann
    • , Che C. Colpitts
    • , Houssein El Saghire
    • , Federica Piccioni
    • , Frank Jühling
    • , Karim Majzoub
    • , Caroline Pons
    • , Charlotte Bach
    • , Julie Lucifora
    • , Joachim Lupberger
    • , Michael Nassal
    • , Glenn S. Cowley
    • , Naoto Fujiwara
    • , Sen-Yung Hsieh
    • , Yujin Hoshida
    • , Emanuele Felli
    • , Patrick Pessaux
    • , Camille Sureau
    • , Catherine Schuster
    • , David E. Root
    • , Eloi R. Verrier
    •  & Thomas F. Baumert
  • Article
    | Open Access

    Immune checkpoint inhibitors have limited efficacy in tumors with lower mutational burden and non-permissive microenvironment. Here, the authors show that combining MEK inhibition with an agonist anti-CD40 immunostimulatory antibody improves antitumor treatment by inducing immunogenic changes in the tumor microenvironment.

    • Daniel Baumann
    • , Tanja Hägele
    • , Julian Mochayedi
    • , Jennifer Drebant
    • , Caroline Vent
    • , Sven Blobner
    • , Julia Han Noll
    • , Irena Nickel
    • , Corinna Schumacher
    • , Sophie Luise Boos
    • , Aline Sophie Daniel
    • , Susann Wendler
    • , Michael Volkmar
    • , Oliver Strobel
    •  & Rienk Offringa
  • Article
    | Open Access

    Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications with limited treatment options. Here the authors show that dysregulation of bile acids increases risk for PTB in pregnant women while restoring bile acid homeostasis delays or prevents PTB in the mouse models.

    • Sangmin You
    • , Ai-Min Cui
    • , Syed F. Hashmi
    • , Xinmu Zhang
    • , Christina Nadolny
    • , Yuan Chen
    • , Qiwen Chen
    • , Xin Bush
    • , Zachary Hurd
    • , Winifer Ali
    • , Gang Qin
    •  & Ruitang Deng
  • Article
    | Open Access

    Murine ILCs can modulate T cell responses in MHCII-dependent manner. Here the authors show that human ILCs process and present antigens and induce T-cell responses upon exposure to IL-1-family cytokines; along with the article by Lehmann et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

    • Anna Rao
    • , Otto Strauss
    • , Efthymia Kokkinou
    • , Mélanie Bruchard
    • , Kumar P. Tripathi
    • , Heinrich Schlums
    • , Anna Carrasco
    • , Luca Mazzurana
    • , Viktoria Konya
    • , Eduardo J. Villablanca
    • , Niklas K. Björkström
    • , Ulrik Lindforss
    • , Hergen Spits
    •  & Jenny Mjösberg
  • Article
    | Open Access

    The molecular mechanisms that drive irreversible acute liver failure remain poorly characterized. Here, the authors show that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage during acute liver injury by blocking restorative neutrophil driven inflammation.

    • Abhishek Chauhan
    • , Lozan Sheriff
    • , Mohammed T. Hussain
    • , Gwilym J. Webb
    • , Daniel A. Patten
    • , Emma L. Shepherd
    • , Robert Shaw
    • , Christopher J. Weston
    • , Debashis Haldar
    • , Samuel Bourke
    • , Rajan Bhandari
    • , Stephanie Watson
    • , David H. Adams
    • , Steve P. Watson
    •  & Patricia F. Lalor
  • Article
    | Open Access

    Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use 1H-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.

    • Kay H. M. Roumans
    • , Lucas Lindeboom
    • , Pandichelvam Veeraiah
    • , Carlijn M. E. Remie
    • , Esther Phielix
    • , Bas Havekes
    • , Yvonne M. H. Bruls
    • , Martijn C. G. J. Brouwers
    • , Marcus Ståhlman
    • , Marjan Alssema
    • , Harry P. F. Peters
    • , Renée de Mutsert
    • , Bart Staels
    • , Marja-Riitta Taskinen
    • , Jan Borén
    • , Patrick Schrauwen
    •  & Vera B. Schrauwen-Hinderling
  • Article
    | Open Access

    Dietary lipids are linked to the development of inflammatory bowel diseases through unclear mechanisms. Here, the authors report that dietary polyunsaturated fatty acids trigger intestinal inflammation resembling aspects of Crohn’s disease, which is restricted by glutathione peroxidase 4 in the intestinal epithelium.

    • Lisa Mayr
    • , Felix Grabherr
    • , Julian Schwärzler
    • , Isabelle Reitmeier
    • , Felix Sommer
    • , Thomas Gehmacher
    • , Lukas Niederreiter
    • , Gui-Wei He
    • , Barbara Ruder
    • , Kai T. R. Kunz
    • , Piotr Tymoszuk
    • , Richard Hilbe
    • , David Haschka
    • , Clemens Feistritzer
    • , Romana R. Gerner
    • , Barbara Enrich
    • , Nicole Przysiecki
    • , Markus Seifert
    • , Markus A. Keller
    • , Georg Oberhuber
    • , Susanne Sprung
    • , Qitao Ran
    • , Robert Koch
    • , Maria Effenberger
    • , Ivan Tancevski
    • , Heinz Zoller
    • , Alexander R. Moschen
    • , Günter Weiss
    • , Christoph Becker
    • , Philip Rosenstiel
    • , Arthur Kaser
    • , Herbert Tilg
    •  & Timon E. Adolph
  • Article
    | Open Access

    The physiological roles of the Golgi reassembly-stacking protein 55 (GRASP55/GORASP55) remain largely elusive. Here, the authors show that the Golgi-resident protein GRASP55 plays a crucial role in lipid homeostasis by regulating intestinal lipid uptake.

    • Jiyoon Kim
    • , Hyeyon Kim
    • , Shin Hye Noh
    • , Dong Geon Jang
    • , Shi-Young Park
    • , Dongkook Min
    • , Hyunki Kim
    • , Hee-Seok Kweon
    • , Hoguen Kim
    • , Sowon Aum
    • , Sookyung Seo
    • , Cheol Soo Choi
    • , Hail Kim
    • , Jae Woo Kim
    • , Seok Jun Moon
    • , Heon Yung Gee
    •  & Min Goo Lee
  • Article
    | Open Access

    Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

    • Qing Ji
    • , Lihong Zhou
    • , Hua Sui
    • , Liu Yang
    • , Xinnan Wu
    • , Qing Song
    • , Ru Jia
    • , Ruixiao Li
    • , Jian Sun
    • , Ziyuan Wang
    • , Ningning Liu
    • , Yuanyuan Feng
    • , Xiaoting Sun
    • , Gang Cai
    • , Yu Feng
    • , Jianfeng Cai
    • , Yihai Cao
    • , Guoxiang Cai
    • , Yan Wang
    •  & Qi Li
  • Article
    | Open Access

    Cases of C. difficile (CD) resistant to metronidazole have been reported but the mechanism remains enigmatic. Here the authors identify a plasmid, which correlates with metronidazole resistance status in a large international collection of CD isolates, and demonstrate that the plasmid can confer metronidazole resistance.

    • Ilse M. Boekhoud
    • , Bastian V. H. Hornung
    • , Eloisa Sevilla
    • , Céline Harmanus
    • , Ingrid M. J. G. Bos-Sanders
    • , Elisabeth M. Terveer
    • , Rosa Bolea
    • , Jeroen Corver
    • , Ed J. Kuijper
    •  & Wiep Klaas Smits
  • Article
    | Open Access

    Here, via a metagenomics analysis of population-based and disease cohorts, Vich Vila et al. study the impact of 41 commonly used medications on the taxonomic structures, metabolic potential and resistome of the gut microbiome, underscoring the importance of correcting for multiple drug use in microbiome studies.

    • Arnau Vich Vila
    • , Valerie Collij
    • , Serena Sanna
    • , Trishla Sinha
    • , Floris Imhann
    • , Arno R. Bourgonje
    • , Zlatan Mujagic
    • , Daisy M. A. E. Jonkers
    • , Ad A. M. Masclee
    • , Jingyuan Fu
    • , Alexander Kurilshikov
    • , Cisca Wijmenga
    • , Alexandra Zhernakova
    •  & Rinse K. Weersma
  • Article
    | Open Access

    Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses.

    • Bojan Losic
    • , Amanda J. Craig
    • , Carlos Villacorta-Martin
    • , Sebastiao N. Martins-Filho
    • , Nicholas Akers
    • , Xintong Chen
    • , Mehmet E. Ahsen
    • , Johann von Felden
    • , Ismail Labgaa
    • , Delia DʹAvola
    • , Kimaada Allette
    • , Sergio A. Lira
    • , Glaucia C. Furtado
    • , Teresa Garcia-Lezana
    • , Paula Restrepo
    • , Ashley Stueck
    • , Stephen C. Ward
    • , Maria I. Fiel
    • , Spiros P. Hiotis
    • , Ganesh Gunasekaran
    • , Daniela Sia
    • , Eric E. Schadt
    • , Robert Sebra
    • , Myron Schwartz
    • , Josep M. Llovet
    • , Swan Thung
    • , Gustavo Stolovitzky
    •  & Augusto Villanueva
  • Article
    | Open Access

    FXR agonists have been investigated for the treatment of non-alcoholic steatohepatitis and liver fibrosis but the clinical efficacy is not optimal. Here the authors show that enhanced FXR SUMOylation in activated hepatic stellate cells reduces FXR signaling and that this can be rescued by SUMOylation inhibitors.

    • Jiyu Zhou
    • , Shuang Cui
    • , Qingxian He
    • , Yitong Guo
    • , Xiaojie Pan
    • , Pengfei Zhang
    • , Ningning Huang
    • , Chaoliang Ge
    • , Guangji Wang
    • , Frank J. Gonzalez
    • , Hong Wang
    •  & Haiping Hao
  • Article
    | Open Access

    Human induced pluripotent stem cell-derived intestinal organoids (HIOs) are powerful tools to study development and diseases of the gastrointestinal tract. Here, the authors develop a directed differentiation protocol to generate mesenchyme-free HIOs that can be patterned towards proximal small intestine or colonic epithelium, and demonstrated their utility in modeling CFTR function.

    • Aditya Mithal
    • , Amalia Capilla
    • , Dar Heinze
    • , Andrew Berical
    • , Carlos Villacorta-Martin
    • , Marall Vedaie
    • , Anjali Jacob
    • , Kristine Abo
    • , Aleksander Szymaniak
    • , Megan Peasley
    • , Alexander Stuffer
    • , John Mahoney
    • , Darrell N. Kotton
    • , Finn Hawkins
    •  & Gustavo Mostoslavsky
  • Article
    | Open Access

    Intestinal aging is associated with declines in structure and absorption of nutrients. Here, the authors show that aging related intestinal decline is mediated by activation of the mTORC1-p38MAPK-p53 pathway in intestinal stem cells and can be ameliorated by abrogating mTORC1 or p38MAPK activity.

    • Dan He
    • , Hongguang Wu
    • , Jinnan Xiang
    • , Xinsen Ruan
    • , Peike Peng
    • , Yuanyuan Ruan
    • , Ye-Guang Chen
    • , Yibin Wang
    • , Qiang Yu
    • , Hongbing Zhang
    • , Samy L. Habib
    • , Ronald A. De Pinho
    • , Huijuan Liu
    •  & Baojie Li
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    • , Andrew T. Gewirtz
    •  & Benoit Chassaing
  • Article
    | Open Access

    The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

    • Jörn F. Ziegler
    • , Chotima Böttcher
    • , Marilena Letizia
    • , Cansu Yerinde
    • , Hao Wu
    • , Inka Freise
    • , Yasmina Rodriguez-Sillke
    • , Ani K. Stoyanova
    • , Martin E. Kreis
    • , Patrick Asbach
    • , Desiree Kunkel
    • , Josef Priller
    • , Ioannis Anagnostopoulos
    • , Anja A. Kühl
    • , Konstanze Miehle
    • , Michael Stumvoll
    • , Florian Tran
    • , Broder Fredrich
    • , Michael Forster
    • , Andre Franke
    • , Christian Bojarski
    • , Rainer Glauben
    • , Britt-Sabina Löscher
    • , Britta Siegmund
    •  & Carl Weidinger
  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    • , Camilla M. Reehorst
    • , Rebecca Nightingale
    • , Irvin Ng
    • , Holly Anderton
    • , Sheren Al-Obaidi
    • , Analia Lesmana
    • , Cameron M. Scott
    • , Paul Ioannidis
    • , Hina Kalra
    • , Shivakumar Keerthikumar
    • , Lars Tögel
    • , Angela Rigopoulos
    • , Sylvia J. Gong
    • , David S. Williams
    • , Prusoth Yoganantharaja
    • , Kim Bell-Anderson
    • , Suresh Mathivanan
    • , Yann Gibert
    • , Scott Hiebert
    • , Andrew M. Scott
    • , Matthew J. Watt
    •  & John M. Mariadason
  • Article
    | Open Access

    The hepatopancreatic ductal (HPD) system connects both liver and pancreas to the intestine but the molecular details of HPD development are unclear. Here, the authors describe how regionalised Eph/Ephrin signaling regulates HPD morphogenesis by promoting cellular rearrangements leading to an open tube.

    • M. Ilcim Thestrup
    • , Sara Caviglia
    • , Jordi Cayuso
    • , Ronja L. S. Heyne
    • , Racha Ahmad
    • , Wolfgang Hofmeister
    • , Letizia Satriano
    • , David G. Wilkinson
    • , Jesper B. Andersen
    •  & Elke A. Ober
  • Article
    | Open Access

    Predicting the drug response of patients with cancer is crucial for implementing targeted therapy. Here, Su et al. make patient-derived cell lines and perform targeted sequencing and RNA-seq to identify CDKN2A/2B loss as a predictor of response to CDK4/6 inhibitors in esophageal squamous cell carcinoma.

    • Dan Su
    • , Dadong Zhang
    • , Jiaoyue Jin
    • , Lisha Ying
    • , Miao Han
    • , Kaiyan Chen
    • , Bin Li
    • , Junzhou Wu
    • , Zhenghua Xie
    • , Fanrong Zhang
    • , Yihui Lin
    • , Guoping Cheng
    • , Jing-Yu Li
    • , Minran Huang
    • , Jinchao Wang
    • , Kailai Wang
    • , Jianjun Zhang
    • , Fugen Li
    • , Lei Xiong
    • , Andrew Futreal
    •  & Weimin Mao
  • Article
    | Open Access

    The role of the transmembrane glycoprotein CD47 in healing injured intestinal mucosa is unclear. Here, the authors show that selective loss of CD47 in the murine intestinal epithelium results in defective mucosal repair after colonic wounding, with suggested impaired cell migration in vitro.

    • Michelle Reed
    • , Anny-Claude Luissint
    • , Veronica Azcutia
    • , Shuling Fan
    • , Monique N. O’Leary
    • , Miguel Quiros
    • , Jennifer Brazil
    • , Asma Nusrat
    •  & Charles A. Parkos
  • Article
    | Open Access

    Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis.

    • Fengjie Huang
    • , Xiaojiao Zheng
    • , Xiaohui Ma
    • , Runqiu Jiang
    • , Wangyi Zhou
    • , Shuiping Zhou
    • , Yunjing Zhang
    • , Sha Lei
    • , Shouli Wang
    • , Junliang Kuang
    • , Xiaolong Han
    • , Meilin Wei
    • , Yijun You
    • , Mengci Li
    • , Yitao Li
    • , Dandan Liang
    • , Jiajian Liu
    • , Tianlu Chen
    • , Chao Yan
    • , Runmin Wei
    • , Cynthia Rajani
    • , Chengxing Shen
    • , Guoxiang Xie
    • , Zhaoxiang Bian
    • , Houkai Li
    • , Aihua Zhao
    •  & Wei Jia
  • Article
    | Open Access

    In a large prospective cohort of liver transplantation (LT) recipients, the authors identify associations between colonization by multidrug-resistant bacteria (MDRB) and microbiome dysbiosis pre- and post-LT, suggesting colonizing MDRB as an important target for microbiome-informed therapeutic approaches post-LT.

    • Medini K. Annavajhala
    • , Angela Gomez-Simmonds
    • , Nenad Macesic
    • , Sean B. Sullivan
    • , Anna Kress
    • , Sabrina D. Khan
    • , Marla J. Giddins
    • , Stephania Stump
    • , Grace I. Kim
    • , Ryan Narain
    • , Elizabeth C. Verna
    •  & Anne-Catrin Uhlemann
  • Article
    | Open Access

    Activated hepatic stellate cells of putative mesodermal origin orchestrate scarring during injury. Here, the authors define a discrete morphologically plastic lineage of embryonic mesothelial-derived scar-orchestrating cells, through a distinct quiescent adult precursor, defined and paradoxically inhibited by WT1.

    • Timothy James Kendall
    • , Catherine Mary Duff
    • , Luke Boulter
    • , David H. Wilson
    • , Elisabeth Freyer
    • , Stuart Aitken
    • , Stuart John Forbes
    • , John Peter Iredale
    •  & Nicholas Dixon Hastie
  • Article
    | Open Access

    Dysfunctional autophagy induces inflammation that contributes to tumorigenesis. Here, the authors show that loss of BRG1 impairs autophagy and enhances reactive oxygen species production to disrupt intestinal barrier integrity, leading to spontaneous colitis and subsequent colorectal cancer development.

    • Min Liu
    • , Tongyu Sun
    • , Ni Li
    • , Junjie Peng
    • , Da Fu
    • , Wei Li
    • , Li Li
    •  & Wei-Qiang Gao
  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is associated with severe neonatal morbidity. Here the authors show, mirroring the NEC phenotype, that IL-23 overexpression in neonates causes malabsorption and decreased expression of intestinal and pancreatic genes mediating food digestion and uptake through IL-22, which directly suppresses pancreatic cell differentiation.

    • Lili Chen
    • , Valentina Strohmeier
    • , Zhengxiang He
    • , Madhura Deshpande
    • , Jovani Catalan-Dibene
    • , Scott K. Durum
    • , Thomas M. Moran
    • , Thomas Kraus
    • , Huabao Xiong
    • , Jeremiah J. Faith
    • , Chhinder P. Sodhi
    • , David J. Hackam
    • , Sergio A. Lira
    •  & Glaucia C. Furtado
  • Article
    | Open Access

    Epithelial turnover in the colon requires stem cells in the crypt that express the R-spondin receptor Lgr5. Here, the authors show that regeneration after colon injury involving loss of Lgr5+ and Axin2+ cells requires stromal derived Rspo3-dependent reprogramming of Lgr4+ differentiated cells, including Krt20+ enterocytes.

    • Christine Harnack
    • , Hilmar Berger
    • , Agne Antanaviciute
    • , Ramon Vidal
    • , Sascha Sauer
    • , Alison Simmons
    • , Thomas F. Meyer
    •  & Michael Sigal
  • Article
    | Open Access

    Retrotransposons are usually dormant in healthy tissue, but become activated during malignancy. Here, in colorectal cancer, Cajuso et al. show that retrotransposon activity associates with clinical features of the disease.

    • Tatiana Cajuso
    • , Päivi Sulo
    • , Tomas Tanskanen
    • , Riku Katainen
    • , Aurora Taira
    • , Ulrika A. Hänninen
    • , Johanna Kondelin
    • , Linda Forsström
    • , Niko Välimäki
    • , Mervi Aavikko
    • , Eevi Kaasinen
    • , Ari Ristimäki
    • , Selja Koskensalo
    • , Anna Lepistö
    • , Laura Renkonen-Sinisalo
    • , Toni Seppälä
    • , Teijo Kuopio
    • , Jan Böhm
    • , Jukka-Pekka Mecklin
    • , Outi Kilpivaara
    • , Esa Pitkänen
    • , Kimmo Palin
    •  & Lauri A. Aaltonen
  • Article
    | Open Access

    BTLA is established as a negative regulator of natural killer T (NKT) cell function, and share its ligand HVEM with CD160. Here the authors show, by analyzing NKT activation in CD160-deficient mice or with BTLA blockade, that CD160 synergizes with BTLA to negatively regulate NKT cells during hepatic injury.

    • Tae-Jin Kim
    • , Gayoung Park
    • , Jeongmin Kim
    • , Seon Ah Lim
    • , Jiyoung Kim
    • , Kyungtaek Im
    • , Min Hwa Shin
    • , Yang-Xin Fu
    • , Maria-Luisa Del Rio
    • , Jose-Ignacio Rodriguez-Barbosa
    • , Cassian Yee
    • , Kyung-Suk Suh
    • , Seong-Jin Kim
    • , Sang-Jun Ha
    •  & Kyung-Mi Lee
  • Article
    | Open Access

    The roles played by thrombin in the human intestinal mucosa are unclear. Here, the authors show that the commensal microbiota modulates epithelial production of active thrombin, which controls biofilm growth and contributes to protection of the mucosa from bacterial invasion.

    • Jean-Paul Motta
    • , Alexandre Denadai-Souza
    • , David Sagnat
    • , Laura Guiraud
    • , Anissa Edir
    • , Chrystelle Bonnart
    • , Mireille Sebbag
    • , Perrine Rousset
    • , Ariane Lapeyre
    • , Carine Seguy
    • , Noa Mathurine-Thomas
    • , Heather J. Galipeau
    • , Delphine Bonnet
    • , Laurent Alric
    • , Andre G. Buret
    • , John L. Wallace
    • , Antoine Dufour
    • , Elena F. Verdu
    • , Morley D. Hollenberg
    • , Eric Oswald
    • , Matteo Serino
    • , Celine Deraison
    •  & Nathalie Vergnolle
  • Article
    | Open Access

    The development of brain metastases is a lethal yet poorly understood event in the evolution of many cancers. Here, the authors perform whole-genome and whole-exome sequencing on matched normal, primary and metastatic tissue samples to explore the genomic features of brain metastases in colorectal cancer.

    • Jing Sun
    • , Cheng Wang
    • , Yi Zhang
    • , Lingyan Xu
    • , Weijia Fang
    • , Yuping Zhu
    • , Yi Zheng
    • , Xiaofeng Chen
    • , Xiju Xie
    • , Xinhua Hu
    • , Weidong Hu
    • , Jingyu Zheng
    • , Ping Li
    • , Jian Yu
    • , Zhu Mei
    • , Xiaomin Cai
    • , Biao Wang
    • , Zhibin Hu
    • , Yongqian Shu
    • , Hongbing Shen
    •  & Yanhong Gu
  • Article
    | Open Access

    Alcoholic hepatitis, a common cause of liver failure, lacks effective treatment. Here, the authors show altered hepatic HNF4a isoform expression and hypermethylation of its target genes in patients. HNF4a dysregulation is improved in vitro by TGFb or PPARg modulation suggesting potential therapeutic avenues.

    • Josepmaria Argemi
    • , Maria U. Latasa
    • , Stephen R. Atkinson
    • , Ilya O. Blokhin
    • , Veronica Massey
    • , Joel P. Gue
    • , Joaquin Cabezas
    • , Juan J. Lozano
    • , Derek Van Booven
    • , Aaron Bell
    • , Sheng Cao
    • , Lawrence A. Vernetti
    • , Juan P. Arab
    • , Meritxell Ventura-Cots
    • , Lia R. Edmunds
    • , Constantino Fondevilla
    • , Peter Stärkel
    • , Laurent Dubuquoy
    • , Alexandre Louvet
    • , Gemma Odena
    • , Juan L. Gomez
    • , Tomas Aragon
    • , Jose Altamirano
    • , Juan Caballeria
    • , Michael J. Jurczak
    • , D. Lansing Taylor
    • , Carmen Berasain
    • , Claes Wahlestedt
    • , Satdarshan P. Monga
    • , Marsha Y. Morgan
    • , Pau Sancho-Bru
    • , Philippe Mathurin
    • , Shinji Furuya
    • , Carolin Lackner
    • , Ivan Rusyn
    • , Vijay H. Shah
    • , Mark R. Thursz
    • , Jelena Mann
    • , Matias A. Avila
    •  & Ramon Bataller
  • Article
    | Open Access

    Trefoil factor 1 (TFF1) is a protein secreted by the gastric mucosa that protects against gastric tumourigenesis. Here, the authors show that TFF1 inhibits the oncogenic inflammatory response and IL-6-mediated STAT3 activation by interfering with the binding of IL6 to its receptor IL6Rα.

    • Mohammed Soutto
    • , Zheng Chen
    • , Ajaz A. Bhat
    • , Lihong Wang
    • , Shoumin Zhu
    • , Ahmed Gomaa
    • , Andreia Bates
    • , Nadeem S. Bhat
    • , Dunfa Peng
    • , Abbes Belkhiri
    • , M. Blanca Piazuelo
    • , M. Kay Washington
    • , Xi Chen Steven
    • , Richard Peek Jr.
    •  & Wael El-Rifai
  • Article
    | Open Access

    Clinical and molecular heterogeneity of ulcerative colitis presents unresolved challenges to identify predictive biomarkers of response to therapies. Here, the authors combine mouse colitis time course with patient biopsy transcriptomes, achieving unsupervised clustering of UC patients correlating with therapeutic outcomes in independent data sets.

    • Paulo Czarnewski
    • , Sara M. Parigi
    • , Chiara Sorini
    • , Oscar E. Diaz
    • , Srustidhar Das
    • , Nicola Gagliani
    •  & Eduardo J. Villablanca
  • Article
    | Open Access

    Distinguishing clinical subtypes of IBD is critical for optimal treatments, outcome prediction, and better understanding of disease pathogenesis. Here the authors phenotype blood and intestinal immune cells by mass cytometry and identify signatures associated with distinct disease states.

    • Samuel J. S. Rubin
    • , Lawrence Bai
    • , Yeneneh Haileselassie
    • , Gotzone Garay
    • , Chohee Yun
    • , Laren Becker
    • , Sarah E. Streett
    • , Sidhartha R. Sinha
    •  & Aida Habtezion
  • Article
    | Open Access

    EZH2-mediated methylatation of histone 3 is essential for immune regulation. Here, the authors show that EZH2 inhibitors attenuate experimental colitis in mice by promoting the development of myeloid-derived suppressor cells, and delay the onset of colitis-associated cancer.

    • Jie Zhou
    • , Shuo Huang
    • , Zhongyu Wang
    • , Jiani Huang
    • , Liang Xu
    • , Xuefeng Tang
    • , Yisong Y. Wan
    • , Qi-jing Li
    • , Alistair L. J. Symonds
    • , Haixia Long
    •  & Bo Zhu
  • Article
    | Open Access

    Immune response against tissue-specific antigens is a hallmark of autoimmunity. Here the authors show that a single autoantigen-based nanomedicine can ameliorate pathology in a broad range of liver autoimmunity models without impairing host defenses, suggesting organ-wide tolerization.

    • Channakeshava Sokke Umeshappa
    • , Santiswarup Singha
    • , Jesus Blanco
    • , Kun Shao
    • , Roopa Hebbandi Nanjundappa
    • , Jun Yamanouchi
    • , Albert Parés
    • , Pau Serra
    • , Yang Yang
    •  & Pere Santamaria
  • Article
    | Open Access

    Hyperspectral imaging (HSI) enables recording both morphological and biochemical information, but image acquisition time and geometric distortions limit its clinical applicability. Here the authors overcome these challenges with an endoscope combining HSI and white light to correct for image distortion during freehand operation.

    • Jonghee Yoon
    • , James Joseph
    • , Dale J. Waterhouse
    • , A. Siri Luthman
    • , George S. D. Gordon
    • , Massimiliano di Pietro
    • , Wladyslaw Januszewicz
    • , Rebecca C. Fitzgerald
    •  & Sarah E. Bohndiek
  • Article
    | Open Access

    The histone variant, H2A.Z is known to regulate gene expression and cell proliferation. Here the authors show that H2A.Z has a central role in the control of intestinal epithelial homeostasis in mice, by preventing terminal differentiation of intestinal progenitors.

    • Jérémie Rispal
    • , Lucie Baron
    • , Jean-François Beaulieu
    • , Martine Chevillard-Briet
    • , Didier Trouche
    •  & Fabrice Escaffit
  • Article
    | Open Access

    Early life stress has been associated with the occurrence of gastrointestinal diseases later in life, but underlying mechanisms remain poorly understood. Here, Wong et al. show that early life stress leads to expansion of intestinal stem cells and their differentiation into serotonin-producing enterochromaffin cells through crosstalk between NGF and Wnt signalling pathways.

    • Hoi Leong Xavier Wong
    • , Hong-yan Qin
    • , Siu Wai Tsang
    • , Xiao Zuo
    • , Sijia Che
    • , Chi Fung Willis Chow
    • , Xi Li
    • , Hai-tao Xiao
    • , Ling Zhao
    • , Tao Huang
    • , Cheng Yuan Lin
    • , Hiu Yee Kwan
    • , Tao Yang
    • , Frank M. Longo
    • , Aiping Lyu
    •  & Zhao-xiang Bian
  • Article
    | Open Access

    Dysregulation of PPARα dependent fatty acid oxidation promotes hepatic steatosis. Here the authors show that GPS2 inhibits PPARα activity and that ablation of GPS2 ameliorates hepatic steatosis in mice.

    • Ning Liang
    • , Anastasius Damdimopoulos
    • , Saioa Goñi
    • , Zhiqiang Huang
    • , Lise-Lotte Vedin
    • , Tomas Jakobsson
    • , Marco Giudici
    • , Osman Ahmed
    • , Matteo Pedrelli
    • , Serena Barilla
    • , Fawaz Alzaid
    • , Arturo Mendoza
    • , Tarja Schröder
    • , Raoul Kuiper
    • , Paolo Parini
    • , Anthony Hollenberg
    • , Philippe Lefebvre
    • , Sven Francque
    • , Luc Van Gaal
    • , Bart Staels
    • , Nicolas Venteclef
    • , Eckardt Treuter
    •  & Rongrong Fan
  • Article
    | Open Access

    Development of cirrhosis in individuals with non-alcoholic fatty liver disease can predict mortality. Here the authors used a unique twin and family cohort to identify a gut microbiome-derived 16sRNA signature that can detect cirrhosis in individuals with non-alcoholic fatty liver disease.

    • Cyrielle Caussy
    • , Anupriya Tripathi
    • , Greg Humphrey
    • , Shirin Bassirian
    • , Seema Singh
    • , Claire Faulkner
    • , Ricki Bettencourt
    • , Emily Rizo
    • , Lisa Richards
    • , Zhenjiang Z. Xu
    • , Michael R. Downes
    • , Ronald M. Evans
    • , David A. Brenner
    • , Claude B. Sirlin
    • , Rob Knight
    •  & Rohit Loomba
  • Article
    | Open Access

    Gluten triggers celiac disease in genetically predisposed individuals, but additional unknown mechanisms are required. Here, the authors show that proteases from Pseudomonas aeruginosa can modulate inflammatory pathways that are relevant to the development of food sensitivities, independently of the trigger antigen.

    • Alberto Caminero
    • , Justin L. McCarville
    • , Heather J. Galipeau
    • , Celine Deraison
    • , Steve P. Bernier
    • , Marco Constante
    • , Corinne Rolland
    • , Marlies Meisel
    • , Joseph A. Murray
    • , Xuechen B. Yu
    • , Armin Alaedini
    • , Brian K. Coombes
    • , Premysl Bercik
    • , Carolyn M. Southward
    • , Wolfram Ruf
    • , Bana Jabri
    • , Fernando G. Chirdo
    • , Javier Casqueiro
    • , Michael G. Surette
    • , Nathalie Vergnolle
    •  & Elena F. Verdu
  • Article
    | Open Access

    Innate lymphoid cells (ILC), including natural killer (NK) cells, are important innate immune regulators. Here the authors show that, in human infant intestines, CD103+Eomes+ NK cells are the predominant ILC population, but are replaced gradually by Eomes+ T cells, while NKp44+ NK cells persist in adult intestines.

    • Adrian F. Sagebiel
    • , Fenja Steinert
    • , Sebastian Lunemann
    • , Christian Körner
    • , Renée R. C. E. Schreurs
    • , Marcus Altfeld
    • , Daniel Perez
    • , Konrad Reinshagen
    •  & Madeleine J. Bunders
  • Article
    | Open Access

    Endoplasmic reticulum (ER) stress has been proposed to play a role in metabolic diseases. Here, Sasako and colleagues identify stromal cell-derived factor 2 like 1 (Sdf2l1) as a regulator of the ER stress response to feeding in the liver, and suggest that its downregulation may promote diabetes and hepatic steatosis in humans.

    • Takayoshi Sasako
    • , Mitsuru Ohsugi
    • , Naoto Kubota
    • , Shinsuke Itoh
    • , Yukiko Okazaki
    • , Ai Terai
    • , Tetsuya Kubota
    • , Satoshi Yamashita
    • , Kunio Nakatsukasa
    • , Takumi Kamura
    • , Kaito Iwayama
    • , Kumpei Tokuyama
    • , Hiroshi Kiyonari
    • , Yasuhide Furuta
    • , Junji Shibahara
    • , Masashi Fukayama
    • , Kenichiro Enooku
    • , Kazuya Okushin
    • , Takeya Tsutsumi
    • , Ryosuke Tateishi
    • , Kazuyuki Tobe
    • , Hiroshi Asahara
    • , Kazuhiko Koike
    • , Takashi Kadowaki
    •  & Kohjiro Ueki
  • Article
    | Open Access

    MicroRNA miR-500a-5p has been linked to oncogenesis but its role in colorectal cancer (CRC) is largely unknown. Here, the authors investigate the role of miR-500a-5p in CRC in vitro and in vivo models and find that miR-500a-5p acts as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis.

    • Weimei Tang
    • , Weijie Zhou
    • , Li Xiang
    • , Xiaosheng Wu
    • , Pei Zhang
    • , Jing Wang
    • , Guangnan Liu
    • , Wenjing Zhang
    • , Ying Peng
    • , Xiaoting Huang
    • , Jianqun Cai
    • , Yang Bai
    • , Lan Bai
    • , Wei Zhu
    • , Hongxiang Gu
    • , Jing Xiong
    • , Chen Ye
    • , Aimin Li
    • , Side Liu
    •  & Jide Wang