Reviews & Analysis

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  • 2021 has been a productive year for fungal research. Key studies focused on intestinal inflammation and inflammatory bowel disease highlight antibody-mediated immunity in control of fungal commensalism, commensal and dietary fungi in intestinal inflammation and wound healing, and the therapeutic potential of transgenic yeast engineered to sense and target factors during intestinal inflammation.

    • Iliyan D. Iliev
    Year in Review
  • Key studies published in 2021 demonstrated mechanisms that drive macrophage–fibroblast pathogenicity in Crohn’s disease, developed multi-omics profiles to predict response to biological therapy, and suggested potential complementary treatments and new therapeutic agents in inflammatory bowel disease (IBD) therapy. These results represent important progress towards precision medicine for patients with IBD.

    • Ren Mao
    • Minhu Chen
    Year in Review
  • In this Review, Chu and Traverso provide an overview of gastrointestinal-based drug delivery, discussing conventional delivery methods and challenges posed by the gastrointestinal tract as a drug delivery environment, as well as emerging technologies.

    • Jacqueline N. Chu
    • Giovanni Traverso
    Review Article
  • In this Perspective, Duan, Young and Schnabl explore the effects of bacteriophages on the gut microbiota and the potential applications of phage therapy for treatment of gastrointestinal diseases. Limitations and challenges of phage therapy for gastrointestinal diseases are also discussed.

    • Yi Duan
    • Ry Young
    • Bernd Schnabl
    Perspective
  • In 2021, transcriptome analysis of the mouse and human gut advanced our understanding of the cellular composition, development and surrounding non-neural context of the enteric nervous system (ENS). A role for the ENS in tuning regulatory T cell proportions contributed insights into the dependency between the ENS, immune system and microbiota.

    • Ulrika Marklund
    Year in Review
  • In 2021, our understanding of resistance to therapy in primary liver tumours improved drastically. By taking a holistic approach, three independent studies have characterized the tumour cell biodiversity across space, time and aetiologies in primary liver cancer, decoding the crosstalk between different cell types within the tumour ecosystem and their individual contributions to therapy resistance.

    • Chantal Desdouets
    • Amaia Lujambio
    Year in Review
  • Autoimmune pancreatitis and IgG4-related cholangitis are frequent manifestations of IgG4-related disease (IgG4-RD). Here, Löhr and colleagues present current understanding of the pathophysiology of IgG4-RD and describe all IgG4-RD manifestations in the digestive tract. Diagnosis, prognosis and treatment of IgG4-RD are also discussed.

    • J.-Matthias Löhr
    • Miroslav Vujasinovic
    • Ulrich Beuers
    Review Article
  • Cancer development is a dynamic evolutionary process. This Review explores the mechanisms underlying clonal expansion and contraction as well as the evolutionary dynamics in Barrett oesophagus and its progression to dysplasia and oesophageal adenocarcinoma. The implications for patient management (including surveillance, risk stratification and therapy) are also explored.

    • Melissa Schmidt
    • Richard J. Hackett
    • Trevor A. Graham
    Review Article
  • Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease with a substantial burden worldwide. In this Consensus Statement, a global multidisciplinary group of experts develop consensus statements and recommendations addressing a broad range of topics on NAFLD to raise awareness and spur action.

    • Jeffrey V. Lazarus
    • Henry E. Mark
    • Ming-Hua Zheng
    Consensus Statement
  • In this Review, Albillos and colleagues describe cirrhosis-associated immune dysfunction (CAID) and its components — systemic inflammation and immune deficiency — as well as the role of CAID in the pathogenesis of acute-on-chronic liver failure. Therapies that aim to modulate CAID are discussed.

    • Agustín Albillos
    • Rosa Martin-Mateos
    • Melchor Álvarez-Mon
    Review Article
  • Humans and their microbiota are intrinsically linked. Owing to dynamic interactions within the gut, nutritional science needs to incorporate the microbiome. This Perspective re-examines the history, rationale and future prospects of chemically defined diets (enteral or parenteral) in relation to the burgeoning understanding of the human microbiota.

    • Tiffany Toni
    • John Alverdy
    • Victoria Gershuni
    Perspective
  • Autoimmune diseases share patterns of gut microbiome perturbation and immune dysregulation linked to intestinal barrier dysfunction. In this Perspective, the authors examine dietary tools for precise engineering of the gut microbiome and discuss the potential for diet-based therapies to modulate host–microbiome interaction in the treatment of autoimmune diseases.

    • Mathis Wolter
    • Erica T. Grant
    • Mahesh S. Desai
    Perspective
  • Coeliac disease is a serious condition and a model disease that can shed light into the mechanisms that underlie autoimmunity and chronic inflammation. This Roadmap summarizes key advances in coeliac disease and provides recommendations from a consensus workshop to address the gaps and opportunities in the pathogenesis, diagnosis and management of coeliac disease, providing a path forward.

    • M. Ines Pinto-Sanchez
    • Jocelyn A. Silvester
    • Elena F. Verdu
    Roadmap
  • Metabolomics and lipidomics approaches are being used to identify biomarkers for nonalcoholic fatty liver disease (NAFLD). This Review discusses the application of metabolomics and lipidomics in clinical studies and in the identification of key metabolic pathway alterations in NAFLD.

    • Mojgan Masoodi
    • Amalia Gastaldelli
    • Matej Orešič
    Review Article
  • The complexity of hepatocellular carcinoma (HCC) hinders effective treatment. Here, Lee and colleagues summarize cancer stem cell (CSC) origin and plasticity, CSC–immune system interactions and the effects of the microenvironmental niche on cancer stemness in HCC. Potential CSC-based therapies for HCC are also presented.

    • Terence Kin-Wah Lee
    • Xin-Yuan Guan
    • Stephanie Ma
    Review Article
  • The gut microbiota is increasingly recognized as an important factor in disease development, progression and treatment response. This Review highlights the promise of strategies that target the gut microbiome in the treatment of disease, including cancer and infectious and metabolic diseases.

    • Daniel A. Schupack
    • Ruben A. T. Mars
    • Purna C. Kashyap
    Review Article
  • Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. This Evidence-Based Guideline presents an international consensus on the prevention of venous and arterial thrombotic events in patients with IBD, and includes 19 recommendations for clinical practice.

    • Pablo A. Olivera
    • Stephane Zuily
    • Laurent Peyrin-Biroulet
    Evidence-based Guidelines Open Access
  • Dietary fibre supports gut health and microbial ecology. Thus, characterizing the effects of inadequate fibre and intake of specific fibre formulations on the gut microbiome provides necessary information to move us towards diet–microbiome target treatments to support health.

    • Hannah D. Holscher
    News & Views