Latest Reviews

  • Review Article |

    This Review describes the pathophysiological roles of peroxisome proliferator-activated receptors (PPARs) in nonalcoholic steatohepatitis and related metabolic diseases, and summarizes the preclinical and clinical data on the use of PPAR agonists to treat nonalcoholic steatohepatitis as part of a systemic metabolic disease.

    • Sven Francque
    • , Gyongyi Szabo
    • , Manal F. Abdelmalek
    • , Christopher D. Byrne
    • , Kenneth Cusi
    • , Jean-François Dufour
    • , Michael Roden
    • , Frank Sacks
    •  & Frank Tacke
  • Perspective |

    Population screening and endoscopic surveillance are widely used for colorectal cancer (CRC) prevention and early diagnosis. This Perspective explores the rationale for and approach to risk stratification for CRC prevention and diagnosis, including the limitations, advantages and future challenges for this approach.

    • Mark A. Hull
    • , Colin J. Rees
    • , Linda Sharp
    •  & Sara Koo
  • Review Article |

    Emerging data have revealed that nonalcoholic steatohepatitis (NASH) and fibrosis are associated with the reactivation of developmental pathways in the liver injury response. This Review describes the role of these pathways in liver development and in the pathogenesis of NASH and fibrosis.

    • Changyu Zhu
    • , Ira Tabas
    • , Robert F. Schwabe
    •  & Utpal B. Pajvani
  • Review Article |

    The management of viral hepatitis in the setting of pregnancy requires special consideration. This Review examines each hepatitis virus individually to address the effect of pregnancy on the natural history of infection and how the viral infections influence maternal and infant outcomes, including mother-to-child transmission.

    • Norah A. Terrault
    • , Miriam T. Levy
    • , Ka Wang Cheung
    •  & Gonzague Jourdain
  • Perspective |

    The global burden of inflammatory bowel disease (IBD) is evolving. This Perspective summarizes the global epidemiology of IBD and its changing burden of disease, postulating that the disease is evolving into four epidemiological stages: Emergence, Acceleration in Incidence, Compounding Prevalence and Prevalence Equilibrium.

    • Gilaad G. Kaplan
    •  & Joseph W. Windsor
  • Review Article |

    Transcriptional regulatory mechanisms have a dual role in specifying intestinal epithelial identity and enabling microbial responsiveness. In this Review, Rawls and colleagues describe what is currently known about the epigenetic patterning and transcription factors responsible for this duality.

    • Jennifer K. Heppert
    • , James M. Davison
    • , Cecelia Kelly
    • , Gilberto Padilla Mercado
    • , Colin R. Lickwar
    •  & John F. Rawls
  • Review Article |

    Inflammatory bowel disease (IBD) has different manifestations and associated risk factors between the sexes. This Review explores the sex-based differences in presentation and management of IBD, as well as insights into sex-based differences in pathogenesis and underlying mechanisms inferred from basic research.

    • Wendy A. Goodman
    • , Ian P. Erkkila
    •  & Theresa T. Pizarro
  • Perspective |

    Therapeutic drug monitoring (TDM) has been suggested as a useful tool for managing patients with inflammatory bowel disease on biologic therapy. This Perspective examines evidence and guidelines related to TDM in inflammatory bowel disease management and also strategies to optimize biologic treatment where TDM is not available.

    • Marjorie Argollo
    • , Paulo Gustavo Kotze
    • , Pradeep Kakkadasam
    •  & Geert D’Haens
  • Review Article |

    Food addiction is an eating behaviour that reflects alterations in brain–gut–microbiome (BGM) interactions and a shift towards hedonic mechanisms. This Review summarizes the physiology of food addiction in obesity as it relates to BGM interactions and provides insights into treatment targets for food addiction aimed at each level of the BGM axis.

    • Arpana Gupta
    • , Vadim Osadchiy
    •  & Emeran A. Mayer
  • Perspective |

    Faecal microbiota transplantation (FMT) has emerged as a successful treatment for recurrent Clostridioides difficile infection. In this Perspective, the authors examine the pharmacology of FMT in treatment of C. difficile infection and consider FMT within a pharmacological framework using the parameters intrinsic to all therapeutics: pharmacy, pharmacokinetics, pharmacodynamics and pharmacotherapeutics.

    • Alexander Khoruts
    • , Christopher Staley
    •  & Michael J. Sadowsky
  • Consensus Statement
    | Open Access

    Gut microbiota can be manipulated to benefit host health, including the use of probiotics, prebiotics and synbiotics. This Consensus Statement outlines the definition and scope of the term ‘synbiotics’ as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in May 2019.

    • Kelly S. Swanson
    • , Glenn R. Gibson
    • , Robert Hutkins
    • , Raylene A. Reimer
    • , Gregor Reid
    • , Kristin Verbeke
    • , Karen P. Scott
    • , Hannah D. Holscher
    • , Meghan B. Azad
    • , Nathalie M. Delzenne
    •  & Mary Ellen Sanders
  • Review Article |

    The liver has a broad range of regenerative capacities. In this Review, Michalopoulos and Bhushan describe the regenerative mechanisms employed by hepatic cells after liver injury as well as the experimental models used to investigate these mechanisms and discuss the clinical implications.

    • George K. Michalopoulos
    •  & Bharat Bhushan
  • Review Article |

    Gastrointestinal dysfunction (including dysphagia and constipation) can occur in Parkinson disease (PD), with evidence that they can arise prior to diagnosis of PD. This Review describes new insights into the mechanisms and pathophysiology of the gastrointestinal involvement of PD, including clinical manifestations.

    • R. Alberto Travagli
    • , Kirsteen N. Browning
    •  & Michael Camilleri
  • Review Article |

    Intestinal epithelial glycosylation is influenced by host genetics, the environment and the gut microbiota. In this Review, Kudelka et al. describe the functions of epithelial glycans and discuss the role of epithelial glycosylation in Crohn’s disease and ulcerative colitis.

    • Matthew R. Kudelka
    • , Sean R. Stowell
    • , Richard D. Cummings
    •  & Andrew S. Neish
  • Viewpoint |

    Viral hepatitis is a global public health problem. In this Viewpoint, we asked a selection of scientists and clinicians working in the viral hepatitis field to provide their opinions on progress and pitfalls towards the 2030 viral hepatitis elimination goals.

    • Andrea L. Cox
    • , Manal H. El-Sayed
    • , Jia-Horng Kao
    • , Jeffrey V. Lazarus
    • , Maud Lemoine
    • , Anna S. Lok
    •  & Fabien Zoulim
  • Review Article |

    Modern therapies for malignant liver tumours integrate neoadjuvant and adjuvant strategies. This broad Review discusses these approaches, including advances in staged surgeries, systemic therapies, ablation therapies and liver transplantation.

    • Henrik Petrowsky
    • , Ralph Fritsch
    • , Matthias Guckenberger
    • , Michelle L. De Oliveira
    • , Philipp Dutkowski
    •  & Pierre-Alain Clavien
  • Review Article |

    Evidence points to a crucial role of necroptosis and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. This Review discusses advances in our understanding of apoptosis, necroptosis and pyroptosis as major cell death pathways that can result in pathophysiological outcomes.

    • Jay V. Patankar
    •  & Christoph Becker
  • Perspective |

    Large-scale datasets of increasing size and complexity are being produced in the microbiome and oncology field. This Perspective discusses the potential to harness gut microbiome analysis, big data and machine learning in cancer, and the potential and limitations with this approach.

    • Giovanni Cammarota
    • , Gianluca Ianiro
    • , Anna Ahern
    • , Carmine Carbone
    • , Andriy Temko
    • , Marcus J. Claesson
    • , Antonio Gasbarrini
    •  & Giampaolo Tortora
  • Consensus Statement
    | Open Access

    Cholangiocarcinoma (CCA) comprises heterogeneous biliary malignant tumours, and their incidence is increasing worldwide. This expert Consensus Statement, endorsed by the ENS-CCA, summarizes the latest advances in CCA, including classification, genetics and treatment, and provides recommendations for CCA management and priorities across basic, translational and clinical research.

    • Jesus M. Banales
    • , Jose J. G. Marin
    • , Angela Lamarca
    • , Pedro M. Rodrigues
    • , Shahid A. Khan
    • , Lewis R. Roberts
    • , Vincenzo Cardinale
    • , Guido Carpino
    • , Jesper B. Andersen
    • , Chiara Braconi
    • , Diego F. Calvisi
    • , Maria J. Perugorria
    • , Luca Fabris
    • , Luke Boulter
    • , Rocio I. R. Macias
    • , Eugenio Gaudio
    • , Domenico Alvaro
    • , Sergio A. Gradilone
    • , Mario Strazzabosco
    • , Marco Marzioni
    • , Cédric Coulouarn
    • , Laura Fouassier
    • , Chiara Raggi
    • , Pietro Invernizzi
    • , Joachim C. Mertens
    • , Anja Moncsek
    • , Sumera Rizvi
    • , Julie Heimbach
    • , Bas Groot Koerkamp
    • , Jordi Bruix
    • , Alejandro Forner
    • , John Bridgewater
    • , Juan W. Valle
    •  & Gregory J. Gores
  • Perspective |

    The COVID-19 pandemic has resulted in changes to the management of patients with inflammatory bowel disease, including major disruptions to endoscopy. This Perspective provides a guide and recommendations for inflammatory bowel disease endoscopy during a global health emergency based on expert experience in Italy and France.

    • Federica Furfaro
    • , Lucine Vuitton
    • , Gionata Fiorino
    • , Stephane Koch
    • , Mariangela Allocca
    • , Daniela Gilardi
    • , Alessandra Zilli
    • , Ferdinando D’Amico
    • , Simona Radice
    • , Jean-Baptiste Chevaux
    • , Marion Schaefer
    • , Stanislas Chaussade
    • , Silvio Danese
    •  & Laurent Peyrin-Biroulet
  • Review Article |

    Single-cell transcriptomic technologies are transforming our understanding of cellular diversity and function in health and disease. This Review discusses how these technologies have been applied in hepatology, advancing our understanding of cellular heterogeneity and providing novel insights into liver biology such as metabolic zonation and the mechanisms underpinning liver regeneration.

    • Prakash Ramachandran
    • , Kylie P. Matchett
    • , Ross Dobie
    • , John R. Wilson-Kanamori
    •  & Neil C. Henderson
  • Review Article |

    Hepatitis B virus (HBV) infection remains a global public health issue. This Review provides insights into the evolution of HBV and discusses the mechanisms by which HBV and hepatitis delta virus diversity occurs and the influence of this diversity on disease progression and treatment response.

    • Peter A. Revill
    • , Thomas Tu
    • , Hans J. Netter
    • , Lilly K. W. Yuen
    • , Stephen A. Locarnini
    •  & Margaret Littlejohn
  • Review Article |

    The neoplastic epithelium of pancreatic cancer exists within a dense stroma that is recognized as a critical mediator of disease progression. This Review discusses our current understanding of the three principal constituents of pancreatic cancer stroma, their effect on the prevalent immune landscape and promising therapeutic targets within this compartment.

    • Abdel N. Hosein
    • , Rolf A. Brekken
    •  & Anirban Maitra
  • Perspective |

    As the number of novel drugs for inflammatory bowel disease (IBD) increases, comparison of therapeutic options has become a key challenge in IBD trials. Here, the authors provide an overview of IBD trial design with a focus on comparative research and the head-to-head trials format.

    • Lieven Pouillon
    • , Simon Travis
    • , Peter Bossuyt
    • , Silvio Danese
    •  & Laurent Peyrin-Biroulet
  • Review Article |

    Irritable bowel syndrome is one of the most common gut disorders worldwide and is defined according to patterns of gastrointestinal symptoms that might be limited in their applicability to all countries and cultures. This Review provides an overview of the global burden of irritable bowel syndrome and discusses the implications for the care of patients worldwide.

    • Christopher J. Black
    •  & Alexander C. Ford
  • Perspective |

    The evidence base for robotic gastrointestinal surgery does not yet support its widespread adoption. Here, Kinross et al. discuss this evidence base and the principles on which future gastrointestinal surgical trials should be based, as well as emerging technologies.

    • James M. Kinross
    • , Sam E. Mason
    • , George Mylonas
    •  & Ara Darzi
  • Review Article |

    Mammalian livers are characterized by an alteration of chromosome numbers, or polyploidy. In this Review, Desdouets and collaborators describe the regulation of polyploidy in liver development and pathophysiology, and discuss the mechanisms of hepatocyte polyploidization and its role in liver tumorigenesis.

    • Romain Donne
    • , Maëva Saroul-Aïnama
    • , Pierre Cordier
    • , Séverine Celton-Morizur
    •  & Chantal Desdouets
  • Review Article |

    The biological effects of cytokines in intestinal homeostasis and disease occur as a result of JAK–STAT signalling. This Review describes the current understanding of JAK–STAT signalling in intestinal homeostasis and inflammatory bowel disease as well as the rationale for therapeutically targeting this pathway.

    • Azucena Salas
    • , Cristian Hernandez-Rocha
    • , Marjolijn Duijvestein
    • , William Faubion
    • , Dermot McGovern
    • , Severine Vermeire
    • , Stefania Vetrano
    •  & Niels Vande Casteele
  • Review Article |

    Rectal cancer treatment has evolved towards a multidisciplinary approach to disease management. This Review examines the essential components of rectal cancer management through a multidisciplinary team, with a focus on the effect of this approach and the elements used for staging and developing the treatment plan.

    • Deborah S. Keller
    • , Mariana Berho
    • , Rodrigo O. Perez
    • , Steven D. Wexner
    •  & Manish Chand
  • Review Article |

    The gut microbiota has been linked to non-alcoholic fatty liver disease (NAFLD), but metabolic confounding factors, such as obesity and diabetes, complicate analysis. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling them from underlying metabolic disorders.

    • Judith Aron-Wisnewsky
    • , Chloé Vigliotti
    • , Julia Witjes
    • , Phuong Le
    • , Adriaan G. Holleboom
    • , Joanne Verheij
    • , Max Nieuwdorp
    •  & Karine Clément
  • Review Article |

    Exclusion diets are popular in the management of irritable bowel syndrome (IBS). This Review outlines the mechanisms by which food might lead to symptoms in IBS and discusses different approaches to how exclusion diets can be evaluated in randomized controlled trials.

    • Paul Moayyedi
    • , Magnus Simrén
    •  & Premysl Bercik
  • Review Article |

    Interactions between intestinal epithelial cells, the gut microbiota and immune cells have a key role in maintaining gut homeostasis. This Review describes how epithelial recognition of bacteria through Toll-like receptors participates in establishing homeostasis, and how dysregulation of these receptors can lead to dysbiosis, increasing susceptibility to colitis and tumorigenesis.

    • Juan F. Burgueño
    •  & Maria T. Abreu
  • Review Article |

    Organoid technology has emerged as a powerful method for studying gastrointestinal cancers. This Review describes organoid models of gastrointestinal cancers, such as colorectal and liver cancer, and discusses how they can be used in basic and translational research in fields such as drug discovery and personalized medicine.

    • Harry Cheuk Hay Lau
    • , Onno Kranenburg
    • , Haipeng Xiao
    •  & Jun Yu
  • Review Article |

    The incidence of early-onset colorectal cancer (in patients <50 years old) is increasing at an alarming rate. This Review highlights potential risk factors and putative mechanisms that drive this disease, and suggests likely areas for fruitful research, including diet, stress and antibiotics.

    • Lorne J. Hofseth
    • , James R. Hebert
    • , Anindya Chanda
    • , Hexin Chen
    • , Bryan L. Love
    • , Maria M. Pena
    • , E. Angela Murphy
    • , Mathew Sajish
    • , Amit Sheth
    • , Phillip J. Buckhaults
    •  & Franklin G. Berger
  • Review Article |

    Alterations in the gut microbiota and metabolite profiles of patients with IBD have been described. In this Review, Lavelle and Sokol discuss these alterations and their pathophysiological basis, and identify future targets for precision therapeutic modulation.

    • Aonghus Lavelle
    •  & Harry Sokol
  • Perspective |

    This Perspective discusses the use of antidepressants in disorders of gut–brain interaction (DGBI) and IBD, focusing on how what we have learnt about the role of antidepressants in DGBI could help optimize the management of IBD.

    • Antonina Mikocka-Walus
    • , Alexander C. Ford
    •  & Douglas A. Drossman
  • Review Article |

    The small intestine is a key site for the absorption of nutrients, including lipids. In this Review, the physiology and biochemistry of intestinal fat absorption during health and disease is discussed, including insights into enterocyte biology and clinical disorders of intestinal fat absorption.

    • Chih-Wei Ko
    • , Jie Qu
    • , Dennis D. Black
    •  & Patrick Tso
  • Review Article |

    KRAS mutations are identified in >80% of patients with pancreatic ductal adenocarcinoma and tend to be associated with reduced overall survival. This Review discusses the role of oncogenic KRAS in the biology, diagnosis, prognosis and treatment of pancreatic cancer.

    • Louis Buscail
    • , Barbara Bournet
    •  & Pierre Cordelier
  • Review Article |

    Radiotherapy is used to treat malignancies including gastrointestinal cancers but resistance to radiation can occur owing to biological alterations within the tumour and/or the surrounding microenvironment. Radiosensitizers are needed to improve treatment response to radiation. This Review discusses strategies being used to enhance radiosensitivity in gastrointestinal cancers according to the hallmarks of cancer.

    • Amy M. Buckley
    • , Niamh Lynam-Lennon
    • , Hazel O’Neill
    •  & Jacintha O’Sullivan
  • Review Article |

    Several big data ‘omics’ studies have analysed hepatocellular carcinoma (HCC). This Review describes omics studies in HCC and their potential in drug discovery and as candidate biomarkers. The application of emerging new artificial intelligence methods in HCC drug discovery is also discussed.

    • Bin Chen
    • , Lana Garmire
    • , Diego F. Calvisi
    • , Mei-Sze Chua
    • , Robin K. Kelley
    •  & Xin Chen
  • Review Article |

    Epigenetic modifications and regulators, including DNA methylation, histone modifications and non-coding RNA species, have key pathophysiological roles in colorectal cancer (CRC). This Review outlines these epigenetic aberrations in CRC and their potential as diagnostic, prognostic and predictive biomarkers and therapeutic targets.

    • Gerhard Jung
    • , Eva Hernández-Illán
    • , Leticia Moreira
    • , Francesc Balaguer
    •  & Ajay Goel
  • Review Article |

    Primary biliary cholangitis (PBC) is a chronic, inflammatory and cholestatic liver disease with a variable rate of progression towards biliary cirrhosis. Here, the authors discuss the current understanding of PBC pathogenesis and highlight implications for new therapies.

    • Aliya F. Gulamhusein
    •  & Gideon M. Hirschfield
  • Perspective |

    An area of research suggests a role for microbiota in the pathogenesis of pancreatic diseases, such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus. In this Perspectives, the authors examine the literature implicating microorganisms in diseases of the pancreas as well as the evidence of an inherent pancreatic microbiota.

    • Ryan M. Thomas
    •  & Christian Jobin
  • Review Article |

    This Review discusses the molecular heterogeneity of hepatocellular carcinoma, the intrinsic and extrinsic factors that stimulate tumour evolution and how this information can be leveraged to improve the clinical management of patients with this disease.

    • Amanda J. Craig
    • , Johann von Felden
    • , Teresa Garcia-Lezana
    • , Samantha Sarcognato
    •  & Augusto Villanueva
  • Review Article |

    IBD treatment has an expanding repertoire of drugs targeting different aspects of the immune response. This Review focuses on unravelling the complexity of mucosal immune responses in IBD pathogenesis and how analytical assays might be harnessed to effectively stratify and individualise IBD therapy.

    • Jonathan L. Digby-Bell
    • , Raja Atreya
    • , Giovanni Monteleone
    •  & Nick Powell