Reviews & Analysis

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  • Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease affecting premature infants and causing substantial morbidity and mortality. This Review highlights key advances in the understanding of how NEC develops, discusses preclinical developments in potential therapies and provides a future outlook for the field.

    • David J. Hackam
    • Chhinder P. Sodhi
    Review Article
  • Multiomics advance our understanding of disease progression and can facilitate drug discovery. In this Perspective, current knowledge and applications of omics platforms in inflammatory bowel disease diagnosis and in identifying risk factors are discussed.

    • Manasi Agrawal
    • Kristine H. Allin
    • Tine Jess
    Perspective
  • The liver microenvironment has a dynamic complexity that has not yet been adequately described. A new omics study sheds light on the hepatic parenchymal and immune cell heterogeneity by focusing on the spatial distribution of myeloid cells and macrophages in homeostasis and nonalcoholic fatty liver disease.

    • Adrien Guillot
    • Frank Tacke
    News & Views
  • In this Review, the authors describe how the chronic inflammatory microenvironment in the gastric mucosal epithelia during Helicobacter pylori infection can stimulate intracellular signalling pathways that lead to the development of gastric adenocarcinoma.

    • Yana Zavros
    • Juanita L. Merchant
    Review Article
  • In this Review, Andersen and colleagues discuss exogenous and endogenous factors responsible for mutational signatures in hepatobiliary cancers such as hepatocellular carcinoma and biliary tract cancers. In addition, they explore the role of mutational signatures in hepatobiliary tumorigenesis.

    • Ekaterina Zhuravleva
    • Colm J. O’Rourke
    • Jesper B. Andersen
    Review Article
  • Intestinal tissue engineering offers a potential therapeutic option for short bowel syndrome. This Review examines the progress in intestinal tissue engineering, discusses the components required for engineered intestinal grafts, preclinical progress and efforts towards clinical translation, including challenges to overcome.

    • Lucinda Tullie
    • Brendan C. Jones
    • Vivian S. W. Li
    Review Article
  • Dysbiotic microbiome signatures are linked to type 2 diabetes mellitus and inflammatory bowel disease activity, relapse risk and treatment response. Here, Metwaly and colleagues review these signatures and discuss why integrative analyses of multi-omics data could generate fresh insight into the mechanisms underlying these diseases.

    • Amira Metwaly
    • Sandra Reitmeier
    • Dirk Haller
    Review Article
  • In this Roadmap, Furth, Sethupathy and colleagues discuss advances in our understanding of the mechanisms and treatments of fibrolamellar carcinoma, a rare hepatic cancer that primarily occurs in adolescents and young adults. Recommendations for future progress in research and clinical trials are proposed.

    • Timothy A. Dinh
    • Alan F. Utria
    • Praveen Sethupathy
    Roadmap
  • A subset of colorectal cancers arises from sessile serrated lesions. Tumorigenesis via the serrated neoplasia pathway is largely unexplored. Now, a new study suggests that this pathway is initiated by gastric metaplasia induced by damage and repair, which is triggered by disadvantageous composition of microbiota in the proximal colon.

    • Joep E. G. IJspeert
    • Evelien Dekker
    News & Views
  • In this Review, Russell and Camargo summarize the role of the Hippo signalling pathway in liver development, homeostasis, regeneration and disease, and discuss development of potential therapeutics for liver diseases such as fibrosis and cancer.

    • Jacquelyn O. Russell
    • Fernando D. Camargo
    Review Article
  • Growing evidence indicates that neutrophils are involved in tumorigenesis, progression and metastasis of hepatocellular carcinoma (HCC). Here, Geh and colleagues summarize neutrophil phenotypes in HCC, describe the pathogenetic mechanisms underlying these contributions of neutrophils to HCC and highlight emerging neutrophil-targeted therapies.

    • Daniel Geh
    • Jack Leslie
    • Derek A. Mann
    Review Article
  • Mechanosensation — detecting mechanical forces and converting them into physiological responses — is important for normal gastrointestinal tract function. Mechanosensation abnormalities are frequently found in gastrointestinal diseases. This Review describes the physical properties of the gut relevant for mechanosensing, as well as the mechanosensory molecules, cells and circuits involved in gastrointestinal tract mechanosensation.

    • Arnaldo Mercado-Perez
    • Arthur Beyder
    Review Article
  • Ceresa et al. discuss machine perfusion technologies for liver preservation and transplantation, including the potential of hypothermic and normothermic machine perfusion to improve preservation time and organ quality, as well as the future applications of perfusion technologies.

    • Carlo D. L. Ceresa
    • David Nasralla
    • Peter J. Friend
    Perspective
  • Despite advances in testing for coeliac disease over the past two decades, awareness of this disease remains suboptimal worldwide. Here, Makharia and colleagues summarize the current knowledge of epidemiology, risk factors, diagnosis and follow-up of coeliac disease and highlight opportunities for future research.

    • Govind K. Makharia
    • Prashant Singh
    • Julio C. Bai
    Review Article
  • Vaccination is a key intervention for the elimination of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections to fulfil the WHO’s 2030 global elimination goal. Innovations in 2021 promise to curb HBV transmission by reducing mother-to-child transmission and enhancing vaccine immunogenicity in at-risk adult groups. Additionally, an HCV vaccination trial was conducted, and there were also advances in our understanding of the immunology underpinning the lack of protection against HCV reinfection.

    • Manal H. El-Sayed
    • Jordan J. Feld
    Year in Review
  • Important colorectal cancer (CRC) studies in 2021, including a new standard of care for first-line treatment of MSI-H–dMMR metastatic CRC, single-cell and spatial analysis of primary tumours and investigations of diet in preclinical models of cancer initiation, have provided novel insights into the CRC immune microenvironment.

    • Karuna Ganesh
    Year in Review
  • Important studies in 2021 demonstrated sophisticated developments in the study of liver fibrosis through omics. Cell-specific mapping, single-cell sequencing and deep-learning systems revealed complex intra-hepatic mechanisms and new computational platforms facilitating the research towards drug discovery in liver disease and in fibrosis.

    • Fiona Oakley
    Year in Review
  • Although nonalcoholic fatty liver disease is the most prevalent liver disease worldwide, there is a paucity of good-quality data on its natural history and most studies to date have reported on retrospective data. Robust data are required to inform regulatory end points, trial design and models of care.

    • Emmanuel A. Tsochatzis
    News & Views