Reviews & Analysis

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.

New findings show that a gut microbiome signature derived from metagenomic and phenomic data can accurately predict nonalcoholic fatty liver disease (NAFLD) in obese women. The data highlight a role for phenylacetic acid, a microbial product of aromatic amino acid metabolism, in the cross-talk between the gut microbiome and the host hepatic phenotype.

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.

Pancreatic cancer is a disease with high tumour heterogeneity and dismal prognosis. There are few therapeutic options and many promising drugs have failed in patients, which makes better models to predict drug efficacy a key research priority. Now, a new study shows that patient-derived organoids can be used for molecular and therapeutic profiling and might be useful to predict clinical responses.

Current approaches to manage decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. Here, Bernardi and Caraceni discuss the shift in focus from individual treatments targeting individual complications to disease-modifying agents able to slow the progression of decompensation.

A new report in Science by Ma and colleagues uncovers the interplay of microbiota-controlled bile acid metabolism and immune responses in the context of primary and metastatic liver tumours in mice. Their findings shed light on the gut–liver axis in hepatic malignancies.

IBD is associated with disruptions to resident microbial populations and inflammatory immune responses; however, little is known about how bacteria influence pathogenic immunity. New research identifies microbially produced ascorbate as a potential drug target to ameliorate disease by inhibiting inflammatory T cell function through altered cellular metabolism.

New findings show that disease-specific T cells that target gluten in patients with coeliac disease persist for decades. The data highlight a central role for a highly select and stable population of T cells in disease persistence and support the feasibility of diagnostics and therapies targeting these cells.

Intraepithelial T cells (IETs) are a unique collection of T cells located at the epithelial barrier. This Review highlights the role of these cells in gut homeostasis and disease, including coeliac disease and IBD. Targeting of IETs in therapeutic interventions is also discussed.

Excess adiposity is a risk factor for many cancers of the gastrointestinal system. In this Review, the authors examine the epidemiological evidence of associations between obesity and gastrointestinal cancer risk and explore the potential mechanisms underlying these relationships.

Current effective treatment options for IBS and other functional bowel disorders are limited. This Review focuses on new and emerging therapies that target the entire symptom complex in these common disorders.

Multiple methods exist to induce liver disease and hepatocellular carcinoma formation in mice. This Review provides an overview of different mouse models of hepatocellular carcinoma, discussing approaches to help choose an appropriate model and highlighting specific concepts for immunotherapy research.

Serrated polyps contribute substantially to the development of colorectal cancer. Unfortunately, our knowledge of the molecular events that drive these lesions is limited. Now, a new study describes an organoid-based mouse model that might accelerate our understanding of the serrated neoplasia pathway.

Gastrointestinal symptoms related to motility and function are common. A broad overview on the clinical measurements and tests of gastrointestinal motility, function and sensitivity is provided in this Review, with insights into applications for patient management.

Mitochondria have many key roles, including in cellular metabolism and cell fate decision. This Review explores the role of mitochondrial function and metabolism in homeostasis of the intestinal epithelium in health and disease, highlighting the involvement of the mitochondrial unfolded protein response.

Growing evidence has associated the gut microbiota with the onset of inflammation, a common feature of both obesity and cancer. Here, Cani and Jordan review the links between the gut microbiota, metabolic disorders and the development of gastrointestinal cancer.