Reviews & Analysis

The year 2022 was notable for substantial research progress related to pancreatic ductal adenocarcinoma (PDAC). The first single-cell and spatial transcriptomic atlases of PDAC were reported, a mechanism for how Schwann cells promote perineural invasion was explored, and, finally, the role of exercise in abrogating immunosuppression was shown.

In this Review, Cowardin, Moore and colleagues discuss advances in our understanding of environmental enteric dysfunction in the context of intestinal adaptation and the gut microbiome during pregnancy, lactation and early childhood.

Various pathways enable communication between the gut and brain, and this communication influences physiology and behaviour. Studies published in 2022 demonstrate how our understanding of several of these pathways is advancing rapidly.

Health care contributes to the climate change burden, and measures should be taken to mitigate these effects. This Perspective discusses the carbon footprint of surgery in gastroenterology and hepatology and offers an overview of sustainable strategies.

In 2022, we witnessed advances in the field of alcohol-related liver disease. Key developments included the discovery of novel proteomics-based biomarkers and potential therapeutic targets that regulate the recognition of molecules derived from gut microbiota to modulate liver injury. Additionally, there have been significant advances in refining selection for liver transplantation in severe alcohol-associated hepatitis.

2022 was a proficuous year in both the nonalcoholic fatty liver disease (NAFLD) and obesity fields. Pharmacological treatment for obesity and NAFLD is moving forward, with the possibility of replacing bariatric surgery, artificial intelligence might help us access the histological effects of new drugs, and there were advances in personalized hepatocellular carcinoma screening in patients with NAFLD.

Intestinal gluconeogenesis (IGN) is a conserved mechanism documented in all vertebrates and it has a crucial role in energy homeostasis and metabolic processes. This Perspective provides an overview of IGN and discusses its importance in natural selection.

Key studies published in 2022 further established the importance of alterations in the gut microenvironment and interactions with the enteric and central nervous systems in symptom generation in irritable bowel syndrome and suggested novel and clinically accessible therapeutic approaches for this large group of patients.

This Review discusses the current and emerging therapeutic landscape for treatment of advanced hepatocellular carcinoma, including molecular-targeted monotherapies, immuno-oncology monotherapies, combination therapies and novel therapeutic approaches.

Advances in artificial intelligence (AI) are changing endoscopy and gastrointestinal surgery, including computer-assisted detection and diagnosis, computer-aided navigation, robot-assisted intervention and automated reporting. This Perspective introduces the role of AI in computer-assisted interventions in gastroenterology with insights on regulatory aspects and the challenges ahead.

Primary sclerosing cholangitis (PSC) is closely associated with inflammatory bowel disease (IBD) and potentially provides unique insights into the gut–liver axis. This Review explores these links and provides an overview of the gut microbiome in PSC, including PSC–IBD, exploring related hypotheses of disease mechanisms.

Gastric and gastro-oesophageal cancer is a leading cause of cancer-related death worldwide with a poor prognosis. This Review provides a comprehensive overview of current treatment strategies set on a molecular basis, and discusses future therapeutic avenues.

Pruritus in cholestatic liver diseases is a frequent symptom that impairs quality of life. This Review describes the mechanisms underlying cholestasis-associated itch, discusses potential pruritogens, and highlights therapeutic approaches to manage pruritus in various conditions, including primary biliary cholangitis, primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy.

The gastrointestinal tract is involved in COVID-19, gastrointestinal symptoms can occur and marked changes in the gut microbiota have been observed. This Perspective highlights interactions between the gut microbiota and SARS-CoV-2 infection and increasing interest in the gut–lung axis.

The use of antibiotics affects the gut microbiota. Fenneman and colleagues discuss the role of antibiotics in the epidemiology and pathogenesis of several inflammatory conditions that involve the digestive tract: types 1 and 2 diabetes, eosinophilic oesophagitis, coeliac disease and inflammatory bowel disease.

Global alcohol consumption has increased in the past two decades and is projected to increase further. In this Review, Loomba and colleagues discuss the global epidemiology of alcohol-associated cirrhosis and hepatocellular carcinoma, including risk factors, trends and projections.

Eosinophilic oesophagitis (EoE) is a chronic inflammatory disease of the oesophagus with distinct clinicopathological features and a relationship to other atopic diseases. This Review provides an updated overview of the pathogenesis and clinical management of EoE and discusses treatment options.

There are limited available treatment options for the management of abdominal pain in irritable bowel syndrome (IBS). This Review provides an overview of the gastrointestinal endocannabinoid system and its potential as a therapeutic target for the treatment of pain in IBS.

Mucus, produced by goblet cells, provides the intestinal tract with an additional layer of protection. This Review discusses the role of mucus and goblet cells in intestinal health and disease, and dissects the underlying regulatory mechanisms.

The influence of nerves on cancer is beginning to be understood. This Review discusses emerging insights into the role of the nervous system in gastrointestinal cancer and of nerves as components of the tumour microenvironment, highlighting underlying mechanisms and its potential as a therapeutic target.