15th anniversary

In this Viewpoint article, we asked a selection of scientists and clinicians in the gut microbiota field to provide their opinions on the major advances in and future directions for research, and the challenges and solutions for translating gut microbiome research to the clinic.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. This Review summarizes the epidemiology, risk factors (including viral hepatitis and NAFLD), molecular profiles and treatment of HCC, providing insights into how the global burden of HCC can be reduced.

This Review summarizes current knowledge concerning the molecular subtyping of pancreatic cancer and explores future strategies using molecular taxonomy to guide therapeutic development and therapy with the overall goal of improving outcomes for this disease.

This Consensus Statement provides a conceptual and methodological framework to expand research on colonic motility in experimental animals and humans. The work is intended to facilitate the development of new drugs for common colonic motility disorders and of appropriate diagnostic and therapeutic algorithms for the management of paediatric and adult patients.

The hepatic consequence of metabolic syndrome and obesity, nonalcoholic fatty liver disease (NAFLD), underlies many cases of hepatocellular carcinoma (HCC). In this Review, the authors discuss NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity.

The authors review the newest data on the gut fungal microbiota. They explore technical aspects of its analysis, how the mycobiome is influenced by immune and environmental factors, including fungi–bacteria interactions, and links between the mycobiota and gut diseases.

Key hepatic functions are expressed non-uniformly across liver lobules, a phenomenon termed zonation. Here, Ben-Moshe and Itzkovitz discuss the principles of liver zonation, the intrinsic and extrinsic factors that dictate zonation patterns and new genomic approaches for studying zonation of parenchymal and non-parenchymal cells

Cholangiocytes, which line the intrahepatic and extrahepatic bile ducts, are specialized cells that regulate bile production and homeostasis. Here, the authors discuss the role of cholangiocytes in development and liver regeneration, inflammation and fibrosis and their interactions with the immune system.

Optogenetic and chemogenetic approaches hold great promise in neurogastroenterological research. In this Review, the authors discuss the advantages and limitations of available tools and cover optimal approaches for targeting specific cell types in the gut.

The stomach responds to injury via two main patterns, the superficial response and the glandular response. In this Review, Sáenz and Mills discuss cellular plasticity and reprogramming in the stomach in the context of disease (such as gastric cancer) and during repair and homeostasis.

Attention has turned to the gut microbiota in liver disease, including alcoholic and nonalcoholic fatty liver disease and hepatocellular carcinoma. This Review describes gut–liver communications, including evidence from animal and human studies, compares conditions within the liver disease spectrum and highlights key points for designing microbiome-based studies for liver disease research.

The intestinal lymphatic vasculature has a range of functions, from maintenance of interstitial fluid balance to transport of antigens, cells, dietary lipids and fat-soluble vitamins. In this Review, Petrova and Bernier-Latmani provide an in-depth overview of intestinal lymphatics, including their roles in human diseases.

Scientific literature is ever-expanding. The need for a filter to keep up-to-date with the key information from this onslaught of data is increasingly important.

Women physicians in gastroenterology and hepatology face unique challenges during their early careers, including implicit biases borne of ingrained gender stereotypes and the imposter syndrome. Addressing perceived biases and promoting leadership at the trainee level is crucial to improving female representation in gastroenterology and hepatology.

To deliver precision therapeutics, microbiome-based medicine will require precision of language, logic and numerical accuracy. Epidemiological lessons of the past suggest that attempts to link almost everything in modern life with the microbiome as a risk factor for disease, without rapprochement with plausible mechanisms, will generate controversy rather than consensus.

Late presentation to hepatitis B virus and hepatitis C virus care is common, hindering global efforts to reduce the morbidity and mortality associated with liver disease. Models of care promoting and simplifying early testing of viral hepatitis are needed if we are to eliminate viral hepatitis as a major public health threat by 2030.

In ulcerative colitis, treating beyond endoscopic healing has shown a reduction of relapse and hospitalization, pushing for histological remission to be embraced in clinical practice and clinical trials. Here, we propose the concept of disease clearance (symptomatic, endoscopic and histological remission) as the ultimate goal in the treatment of ulcerative colitis.

Important studies published in 2018 highlight novel therapeutic strategies along the disease course of IBD, including potential specific dietary modifications at early stages and treatment with adipose-derived stem cells in perianal Crohn’s disease. A treat-to-target approach that involves proactive serial monitoring of inflammatory biomarkers can assist in timely treatment escalation and promises improved patient outcomes.

Globally, alcohol is the biggest single preventable factor causing premature death and disability in adults aged 15–49 years. In this Perspective, Gilmore and colleagues summarize the evidence behind alcohol-related public health policies, including those targeting price, availability and marketing of alcohol, and assess their effectiveness.

The many gaps in our knowledge and understanding of HBV infection hampers our ability to develop and achieve a cure on a global scale. In this Perspective, Fabien Zoulim and colleagues propose the development of an international group consisting of four working groups (virology, immunology, innovative tools and clinical trials) to tackle the big questions and make important steps towards eradicating this disease.

In the past few years, data obtained from work in animal models, human genetics, basic science and clinical trials, has provided new insights into the mechanisms underlying Crohn's disease and ulcerative colitis. In this review, the author discusses the evidence underlying the disparate theories on the pathogenesis of these diseases and attempts to reconcile them into a coherent hypothesis based on the experimental data.

IBS is a major drain on health-care resources, partly because the pharmacological management of this condition is currently unsatisfactory. Cognitive behavioral therapy, psychotherapy and hypnotherapy can help by providing a global therapeutic approach for IBS. This Viewpoint article discusses the available evidence for these behavioral therapies and highlights the benefits and the difficulties of using such approaches.

To practice evidence-based medicine, clinicians need to apply the findings of scientific research to the circumstances of individual patients as part of the process of clinical decision-making. This Review article presents a 10-step guide to the critical appraisal of research literature to assist clinicians with the task of identifying the most relevant, high-quality studies available to guide their practice.

The human gut harbours a vast array of micro-organisms and the benefits of these bacteria should not be forgotten. Here, Flint and colleagues discuss the role of the gut microbiota in nutrition and health, describing the development of these bacteria in the healthy gut, and their positive influences on microbial and human metabolism.

Neurogastroenterology encompasses control of digestion through the enteric nervous system, the central nervous system and integrative centers in sympathetic ganglia. In this Review, John Furness provides a broad overview of the rapidly developing field of neurogastroenterology, with a focus on the roles of the enteric nervous system in the control of the musculature of the gastrointestinal tract and transmucosal fluid movement.

Liver transplantation has progressed from an experimental procedure to routine operation since the first human liver transplantation in 1963. This Timeline article revisits the important milestones in the development of liver transplantation, discussing how the procedure has evolved over time and what challenges are still to overcome.

Probiotics are widely regarded as live microorganisms that, when administered in sufficient amounts, confer a health benefit, but guidance is needed on the most appropriate use of the term. This Consensus Statement outlines recommendations for the scope and definition of the term 'probiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in October 2013.