Review Articles in 2021

This Review explores how the gut microbiota acts as a driver and regulator of host circadian rhythms and metabolism, highlighting its unique role in transducing dietary cues. Key determinants of microbial oscillations and insights into microbial control of chronometabolism are discussed.

Pancreatic cancer is a leading cause of cancer death worldwide. This Review outlines the current knowledge of established pancreatic cancer risk factors, including lifestyle and inherited risk factors.

Chemokines have an important role in liver diseases such as alcohol-associated liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma. This Review describes the regulation of chemokines in the liver, their roles in liver diseases and the potential therapeutic targets.

This Review describes the evidence of an association and causal link between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), discusses their pathophysiological mechanisms and summarizes the pharmacological treatments that might benefit or adversely affect the risk of T2DM or NAFLD progression.

Immunotherapeutic interventions might be effective tools for the treatment of hepatocellular carcinoma. This Review provides up-to-date information on the clinical use of currently available immunotherapies in hepatocellular carcinoma, the mechanisms of response and resistance, and the therapeutic strategies under development.

Aryl hydrocarbon receptor (AHR) signalling has important roles in the intestine. In this Review, Stockinger, Shah and Wincent discuss AHR regulation, its role in various intestinal cell types and in intestinal inflammation and tumorigenesis.

Pancreatic ductal adenocarcinoma (PDAC) has a unique tumour microenvironment. Notably, PDAC can reprogramme metabolism in response to this microenvironment. This Review discusses metabolism in pancreatic cancer, including insights into mechanisms and processes as well as the potential therapeutic applications.

Enteric glia regulate homeostasis in the enteric nervous system and influence gastrointestinal function. This Review provides an update on enteric glial biology and the underlying mechanisms by which enteric glia regulate gastrointestinal function and disease, with a focus on neuronal and immune interactions.

Evidence suggests that ileal Crohn’s disease is distinct from colonic Crohn’s disease on a multitude of layers. This Review provides a structured overview of this evidence and its implications for clinical decision-making.

This Review provides mechanistic and clinical insights into COVID-19 in the context of liver disease, discussing the potential underlying biology and clinical features of SARS-CoV-2 infection in patients with pre-existing liver conditions. The management of these patients is also discussed, including SARS-CoV-2 vaccination strategies.

Oesophageal cancer is a global health problem with two main histological subtypes, oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. This Review establishes the current epidemiology of oesophageal cancer, with a particular focus on the increasing incidence of oesophageal adenocarcinoma and its precursor, Barrett oesophagus.

Liver sinusoidal endothelial cells (LSECs) form the wall of the hepatic sinusoids and have essential roles in hepatic homeostasis. This Review describes the phenotypic dysregulations of LSECs in the context of liver disease and hepatocellular carcinoma, and provides an update of the role of LSECs as therapeutic targets.

The therapeutic pipeline for nonalcoholic steatohepatitis (NASH) is expanding as insights into disease pathophysiology are gained. This Review summarizes progress in the development of NASH therapies, current and ongoing clinical trials, and potential challenges with emerging therapies.

Farnesoid X receptor (FXR) is involved in the control of bile acid synthesis and enterohepatic circulation. This Review discusses the role of FXR in metabolic diseases and gastrointestinal and liver cancers, highlighting underlying mechanisms and potential therapeutic targets.

Many molecular, physiological and behavioural processes display distinct daily rhythms that are directed by the circadian system. This Review summarizes knowledge about the diurnal regulation of gastrointestinal processes by circadian clocks present in the digestive tract and its accessory organs, including circadian control of digestion, motility, hormones, barrier function and the gut microbiota.

Although the role of the enteric nervous system in congenital enteric neuropathic disorders is well acknowledged, its role in systemic diseases is less understood. Here, the authors focus on diseases in which the enteric nervous system has so far not been considered to have a major role and on its emerging role in neurodegeneration, cancer and diabetes.

In this Review, Motta, Vergnolle and colleagues describe the organization of microorganisms into planktonic, biofilm and biofilm-dispersed forms in the gastrointestinal tract. The role of the host–biofilm relationship in gut homeostasis and disease is discussed.

Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of hepatocellular carcinoma. This Review analyses data from randomized and uncontrolled studies reported with ablative and locoregional techniques and examines the expected effects of combinations with systemic treatments, exploring their distinct mechanisms of action.