Review Articles in 2018

Liver microcirculatory dysfunction is one of the key mechanisms that promotes the progression of chronic liver disease. In this Review, the authors explore the role of liver microcirculatory dysfunction in cirrhotic portal hypertension, the preclinical models used to study liver circulation and potential therapeutics.

Fatigue is an important problem for patients with IBD, but little is known about its pathophysiology. In this Review, the authors explore the epidemiology, putative mechanisms and optimal management of this symptom.

The liver is a key metabolic organ, and alterations to hepatic metabolism are important for the development of disease. In this Review, the authors explore the central roles of peroxisome proliferator-activated receptor-γ coactivators (PGC1s) in physiological and pathophysiological settings, with a focus on nonalcoholic fatty liver disease and liver cancer.

In this Review, Yadav and Petrov discuss the most up-to-date epidemiological data on acute and chronic pancreatitis. The authors also present strategies to reduce the burden of pancreatitis and its associated metabolic disorders.

The pathophysiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is not yet completely understood but innate immunity is a major factor. In this Review, the evidence for macrophage involvement in the development of liver steatosis, inflammation and fibrosis is discussed.

This Review outlines the current understanding of IL-12 and IL-23 biology in IBD, as well as the roles of major downstream cytokines, including IL-17. The authors also discuss how emerging knowledge influences the development of therapeutic strategies in IBD.

The Wnt–β-catenin pathway is a highly conserved pathway that regulates embryogenesis and key regenerative processes in adult organs. Here, the authors discuss the role of Wnt–β-catenin signalling in liver development and disease, including in liver cancer, NAFLD and liver fibrosis.

Redox signalling in the gastrointestinal mucosa is held in an intricate balance. This Review addresses both the spectrum and intensity of redox activity pertaining to host–immune and host–microbiota crosstalk during homeostasis and disease processes in the gastrointestinal tract.

The intestinal epithelium undergoes constant replenishment, fuelled by continuously dividing stem cells residing in crypts. In this Review, Gehart and Clevers discuss the signals, cell types and mechanisms that control intestinal stem cell homeostasis and explore how imbalance in key signalling pathways can cause disease.

Electric stimulation of nerves might be useful for various gastrointestinal disorders. In this Review, the authors discuss neuromodulation therapies in relation to current knowledge of the nerve circuitry, provide insights into possible mechanisms and explore reasons for limited success and how effectiveness might be improved.

An association between obesity and many cancers exists, but how obesity affects the tumour microenvironment remains poorly understood. This Review explores key pathways linking visceral obesity and gastrointestinal cancer, including inflammation, hypoxia, stromal and immune cell function, metabolism and angiogenesis.

Current nutritional approaches to prevent and treat various diseases have limited effectiveness. Here, Zmora et al. review the major principles underlying effects of dietary constituents on the gut microbiota, resolving aspects of the diet–microbiota–host crosstalk, and present the promises and challenges of incorporating microbiome data into dietary planning.

Cell death is a fundamental driver of liver disease progression. Here, the authors summarize the specific roles of apoptosis and necroptosis in different liver disease aetiologies, including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and liver cancer.

In this Review, the authors discuss how the gut microbiota might incite food sensitivity. They focus on direct and indirect mechanisms involving microorganisms and how increased understanding of these mechanisms will help the development of therapeutic strategies for food sensitivities.

Metabolic homeostasis is orchestrated partly in response to nutrient-dependent vagal afferent signals transmitted from the gut to the central nervous system. This Review highlights our understanding of the vagal afferent system and its role in regulation of appetite and glucose homeostasis.

Inflammasome signalling has a central role in the regulation of gastrointestinal health and disease. Here, an overview of inflammasome biology in relation to the gastrointestinal tract is presented, with insights into how targeted interventions might be useful to treat inflammasome-mediated gastrointestinal diseases

Metabolic surgery is the best treatment for long-term weight loss maintenance and comorbidity control. In this Review, the authors discuss how gut physiology adapts to these procedures and the consequent effects on food intake, weight loss, liver disease and cancer.

Intervention studies have helped characterize the potential mechanisms linking obesity and risk of gastrointestinal cancers in humans. Here, the authors explore the findings of these trials and detail how the key pathways involved, including inflammation, adipokines and metabolic dysfunction, might modulate carcinogenesis in gastrointestinal tissues.

Liver diseases exert a substantial disease burden across the Asia–Pacific region. In this Review, the authors explore the epidemiological trends in the most common liver diseases in the region, including HBV infection, HCV infection and nonalcoholic fatty liver disease, and discuss implications for preventive measures.

In this Review, the authors summarize how various interactions at the gastrointestinal epithelium regulate gut physiology. They also discuss how neuroimmunophysiology has advanced the understanding of gastrointestinal pathophysiology with the potential to reveal novel therapies for disorders such as IBS and IBD.