Reviews & Analysis

In this Review, Neufert and Neurath discuss the pathophysiological mechanisms of colitis-associated colorectal cancer, focusing on the tumour epithelium, stromal cells, mucosal barrier and mechanisms of tumour development. They also discuss potential implications for personalized therapy.

In this Perspective, Iacucci and colleagues describe the role of artificial intelligence in inflammatory bowel disease care, highlighting emerging applications as well as implications for implementation.

Current drug approvals reshape metabolic dysfunction-associated steatohepatitis (MASH) therapeutic strategies. This Review highlights current and emerging therapeutic targets and discusses a mechanism-based framework for personalized, combination-oriented management in MASH.

‘Gut health’ is a widely used term, but there is much uncertainty and inconsistency related to its use. An international panel has now provided a definition that includes consideration of both gastrointestinal function and symptom burden. While advancing the field, the definition also prompts a number of areas of debate.

Metabolites are important mediators of metabolism at the cellular and organismal levels. This Review explores the concept of metabotherapy, harnessing metabolites to prevent and treat gastrointestinal disorders, providing insights into metabolite classifications and their pathophysiological mechanisms in health and disease and mapping their potential as therapeutic targets.

This Consensus Statement provides a definition of the term ‘gut health’, as well as a discussion of the relevant domains that contribute to gut health and a framework for appropriate use of the term in the context of therapeutic interventions.

Steatotic liver diseases affect millions worldwide through alcohol and metabolic insults. This Review highlights steatotic liver disease genetic architecture, how it informs disease biology, drug discovery and risk stratification through polygenic risk scores and the need for improved clinical applications.

Steatotic liver disease (SLD), which might lead to cirrhosis and hepatocellular carcinoma, is on the rise worldwide. This Expert Recommendation draws on lessons learned to tackle viral hepatitis and proposes a framework for SLD screening and testing policies.

Preclinical models are essential to study disease pathogenesis and test novel treatments. Here, a broad overview of metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models is provided, detailing main features, advances and limitations of in vitro and in vivo models, and how they translate to human disease.

Protein is an essential nutrient in the human diet. This Review explores the fate of dietary protein in the gastrointestinal tract and its influence on colonic health and disease, providing insights into dietary protein metabolism, digestion, absorption, fermentation and the implications for colonic health.

Some of the highlights in the pancreatic cancer field in 2025 include long-term data on personalized neoantigen vaccine approaches in resected pancreatic adenocarcinoma, detailed clinico-genomic analyses of large clinical trial datasets, and therapeutic strategies for early-stage disease.

In this Review, Brown and colleagues describe the latest insights into the role of cholesterol synthesis and metabolism in the gut and liver, and implications in diseases such as metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma and colorectal cancer.

Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis. This Review provides an update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF.

Glycans are essential components of the gut mucosa that modulate epithelial barrier integrity, host–microbiota interactions and gut immune response. This Review discusses the role of mucosal glycans in gut homeostasis, in intestinal inflammation and their therapeutic potential for inflammatory bowel disease.

Gastric and gastroesophageal junction adenocarcinoma remains a major global health challenge, with a rising incidence among younger individuals worldwide despite advances in biomarker-directed targeted therapies and immunotherapy. Current breakthroughs include perioperative immunotherapy, HER2-directed therapy sequencing and a decisive shift towards biomarker-driven treatment.

Chronic hepatitis B infection remains the dominant aetiology of liver-related complications and hepatocellular carcinoma. In 2025, key evidence emerged supporting the expansion of treatment criteria, confirming the feasibility of an RNA interference-based combination regimen to boost functional cure rate, and identifying low-risk individuals who might not require liver cancer surveillance.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

In this Review, Altier and colleagues describe the mechanisms of chronic abdominal pain in inflammatory bowel disease (IBD). In addition, they discuss implications for IBD treatment and identify directions for future research.

In summary, 2025 has seen a shift in focus from pure therapeutic management to active disease prevention. The message is unambiguous. The next breakthrough in IBD will not emerge solely from new drugs or biologics, but from reimagining how we live, eat and engage with the microbial ecosystems that define our health.

Individuals living with human immunodeficiency virus infection are experiencing an increase in liver disease burden. This Review summarizes current knowledge on the burden of liver diseases in this population and provides insights into clinical management and future directions.