Reviews & Analysis

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.

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.

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.

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.

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.

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.

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.

This Perspective highlights an accumulating body of literature that outlines a direct role for oral-associated bacteria in inflammatory bowel disease pathogenesis. The authors propose a model by which oral-associated species might expand in the inflamed intestinal environment to exacerbate inflammation.

Defaecation is a coordinated process that requires a morphologically intact gastrointestinal tract and the integration of multiple physiological systems (neuromuscular, hormonal and cognitive). This Review describes the physiology of human defaecation and continence, providing insights into the pathophysiology of defaecation and evacuation disorders.

Here, the authors describe the complex role of regulated cell death (RCD) in pancreatic tumorigenesis and treatment. They also discuss how RCD is reshaped in tumours at both molecular and metabolic levels and highlight the challenges and opportunities in this field.

Gene editing to correct inherited liver disorders has promise for future therapeutic intervention, but lack of effective and safe delivery of the gene-editing machinery to hepatocytes complicates its clinical application. Two studies now report efficient delivery to the liver of non-human primates, providing proof of concept for novel treatment of inherited hypercholesterolaemia.

Colorectal cancer screening has a large potential to reduce incidence and mortality, and screening programmes have been implemented in many countries and regions. Emerging epidemiological trends and evidence on the effectiveness and cost-effectiveness of various screening options call for regular updates of screening recommendations.

This Review discusses the role of dietary fats and carbohydrates in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Studies on the dietary habits of patients with NAFLD, and the effect on liver fat accumulation of altering dietary macronutrients, are also reviewed.

In this Review, the authors describe the biology of IL-6 family cytokines relevant to metabolism, liver disease and gastrointestinal disease, and discuss the potential of IL-6 family members as therapeutic agents in these areas.

In this Review, Neurath discusses the implications of COVID-19 on immunosuppressive and biologic therapies as well as those of vaccination in gastrointestinal contexts such as inflammatory bowel disease, autoimmune hepatitis and liver transplantation.

There is a need for effective models of care for patients with non-alcoholic fatty liver disease (NAFLD). In this Expert Recommendation, Lazarus et al. discuss seven examples of comprehensive NAFLD models of care and produce eight recommendations aimed at policy-makers and practitioners.

Delineation of fibroblast heterogeneity has the potential to identify select mesenchymal populations involved in health and disease. A recent study integrated single-cell transcriptomic data to generate a fibroblast atlas of steady-state and perturbed tissues in mice and humans, showing baseline and context-specific fibroblast phenotypes between species and pathologies, including IBD.

This Review describes how functional genetic screens can shed light on various outstanding questions in liver cancer biology, including which genes can drive hepatocarcinogenesis, how to improve the efficacy of existing therapies and how to find novel therapeutic targets for liver cancer.

Pancreatic cancer is typically diagnosed at a late stage and early detection is a priority. This Review focuses on precancerous lesions of the pancreas, describing their pathological and molecular features and highlighting different DNA-based molecular approaches for early detection and their clinical utility.

Vast developments are being made within the field of pancreatic cancer genomics. This Review discusses the wide-ranging and most current research with the goal of integrating this information into a unifying description of the life history of pancreatic cancer.