Key Advances in Gastroenterology & Hepatology

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.

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 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.

The year 2025 has seen substantial advances in the understanding and management of metabolic dysfunction-associated steatotic liver disease, providing new insights into its systemic effects. Emerging evidence in 2025 supports integrated heart–liver co-management, translating the concept into actionable clinical strategies.

The gut microbiome presents in a multi-kingdom form and tunes host health in various ways. Studies published in 2025 have further pushed this frontier by unveiling the enigmatic roles of the gut fungi and bacteria in cross-organ regulations of host homeostasis through metabolite and immune cell-mediated pathways.

Pancreatic cancer remains one of the most challenging malignancies, with a very poor prognosis. Current research is focused on elucidating the role of the tumour microenvironment and the microbiome in the development and progression of the disease, as well as on the promising potential of artificial intelligence for early diagnosis and outcome prediction.

In 2024, there were major advances in inflammatory bowel disease research. Treatment strategies with biologic agents for inflammatory bowel disease matured, and gut microbiota–bacteriophage–host interaction emerged as a new frontier to target.

Colorectal cancer remains a challenging heterogeneous disease with substantial morbidity and mortality. However, progressive advances over the past year have led to marked improvements and overcome challenges previously considered insurmountable. Here, we review key clinical trials in colorectal cancer in 2024, leading to personalized approaches in locally advanced and metastatic disease.

Advances in 2024 have transformed our understanding of CD8⁺ T cell dysfunction in chronic hepatitis B virus infection, revealing diverse T cell populations that defy the classic exhaustion model. Studies highlight new therapeutic strategies, such as 4-1BB agonism and TGFβ inhibition, that could rejuvenate these cells and restore antiviral function.

In 2024, important studies highlighted the ongoing global battle against liver cancer, a deadly yet common cancer. Despite advances in treatments, obstacles persist in early detection and equity in healthcare access. The journey towards improving patient outcomes remains bumpy. Gaining insights from failures is critical for effectively tackling this persistent health threat.

The year 2024 was momentous for metabolic dysfunction-associated steatotic liver disease (MASLD): the approval of the first medication for treatment of at-risk metabolic dysfunction-associated steatohepatitis, updated guidelines on the screening, diagnosis and treatment of MASLD, and liver stiffness measurement as an important surrogate marker for liver-related outcomes in MASLD.

The microbiota is critical for metabolic health. Studies published in 2024 have revealed mechanisms by which key bacterial and micro-eukaryotic organisms optimize energy production in our body and ensure efficient metabolic function.

2023 was the most memorable year on record for obesity. The American Academy of Pediatrics recognized the complex, multifactorial nature of obesity and the broad range of treatments necessary to care for pediatric patients. The first-ever triple agonist and high-potency oral GLP1 agonist was introduced with unprecedented results.

In 2023, there were significant advancements in trials of interventions to reduce mortality and morbidity from alcohol-related liver disease, spanning the entire spectrum of disease: primary prevention to reduce overall alcohol-related harm, secondary prevention to attenuate fibrosis progression and tertiary prevention using antibiotics for severe alcohol-associated hepatitis.

Metastatic colorectal cancer is a heterogeneous disease associated with poor patient outcomes. Although the past decade has seen few first-line treatment advances, key studies published in 2023 established new options for late-line therapy of the disease with and without oncogenic drivers, thus expanding the continuum of care in metastatic colorectal cancer.

Important studies published in 2023 outlined new agents and strategies for the management of inflammatory bowel disease. Therapeutic ambitions for the management of inflammatory bowel disease were raised by the success of combinations of biologic agents in ulcerative colitis and early surgical resection in Crohn’s disease.

New light is being shed on the interactions between the gut microbiome, cancer cell signalling and the host immune response. With this knowledge, microbiota-based approaches for improving cancer prevention, prognostication and therapy have started to materialize and will contribute to reducing the global cancer burden.

In 2023, we witnessed advances in allocation policies and marginal donors, including living donors. Key improvements included the uncapped Model for End-stage Liver Disease 3.0 score, unveiled machine perfusion trials to standard deceased donors and lessons from the aborted living donor liver transplantations.

Enteric nervous system function is essential for survival. Studies published in 2023 have provided important novel insights into the mechanisms that regulate its development and maintenance, and demonstrate how it can be restored when these mechanisms fail.

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.

The gut virome is a complex ecosystem and has a critical role in human health. This Review outlines gut virome composition and functional relevance, and its role in human health and disease. Methodological challenges in advancing our knowledge of the gut virome are also discussed.

The gut microbiome has been associated with pancreatic cancer. This Review summarizes the latest findings of microbiota association studies of tumours of the pancreas and outlines the mechanisms as to how the microbiome influences pancreatic cancer and the clinical potential of harnessing the microbiome in pancreatic cancer.

In this Review, Marques and colleagues discuss the evidence regarding the effects of parental diet on the health of offspring, with a focus on how changes to the gut microbiome alter epigenomic responses in the offspring.

Artificial intelligence (AI) is a powerful tool that could be applied to microbiome research. This Perspective discusses best practices and current limitations with the application of AI in microbiome data research, giving insights into future use and practical advice and recommendations on its use.

The global burden of inflammatory bowel disease (IBD) is shifting as countries transition through four epidemiologic stages. This Perspective explores the global evolution of IBD over the next 20 years and proposes strategies for prevention and health-care innovation.

In this Review, Yu and colleagues describe the role of the gut microbiome and the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD-related hepatocellular carcinoma (HCC). They discuss clinical implications for the diagnosis and treatment of MASLD and MASLD-related HCC.

In this Review, Sanz and colleagues discuss how diet shapes the gut microbiome, the role of diet–microbiome interactions on the immune, nervous and cardiometabolic systems, and implications for dietary guidelines and precision nutrition.

Inflammatory bowel disease (IBD) is an immune-mediated disease with substantial burden worldwide. In this Consensus Statement, a global multidisciplinary group of experts identify key priorities and recommendations to raise awareness and advance IBD care and research.

In this Review, Abken provides an overview of clinical trials exploring the use of chimeric antigen receptor (CAR) T cells in gastrointestinal cancers, including colorectal, pancreatic, gastric and oesophageal cancers. Limitations and strategies to overcome challenges are discussed.

Helicobacter pylori has a role in gastric carcinogenesis, among other bacteria. This Review elucidates the role of pathogenic microbes in gastric cancer development and provides valuable insights into the underlying mechanisms.

This Review discusses the link between metabolic dysfunction-associated steatotic liver disease (MASLD) — a heterogeneous health condition — and hepatic and extrahepatic disease manifestations and provides a comprehensive platform for personalized, holistic management for patients with MASLD.

The management of inflammatory bowel disease (IBD) continues to evolve. This Review is a practical guide on the therapeutic toolkit for IBD, with a focus on current and emerging IBD medications, how they relate to management strategies beyond drugs and the importance of the clinician–patient relationship.

In this Viewpoint, Maria Carmen Collado, Suzanne Devkota and Tarini Shankar Ghosh comment on the past and future of gut microbiome research and clinical applications.

Crohn’s disease, a chronic inflammatory bowel disorder, is caused by genetic and environmental factors disrupting gut homeostasis. This Review describes the role of pathobionts in the development of Crohn’s disease, highlighting known mechanisms, genetic mutations affecting homeostasis and potential microbiome-based therapeutic strategies.

In this Viewpoint, Alina M. Allen, Juan Pablo Arab and Vincent Wai-Sun Wong reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing worldwide, and a crucial risk factor is food insecurity. This Review provides an extensive overview of food insecurity in the context of MASLD and discusses potential policies and procedures as interventions.

Many aspects of the biology and pathogenesis of hepatitis E virus (HEV) infection remain underexplored. In this Review, Steinmann and colleagues summarize the role of the innate and adaptive immune systems in HEV infection.

This Perspective discusses the nomenclature change from nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) and proposes steps necessary to improve care and end the public health threat posed by MASLD and metabolic dysfunction-associated steatohepatitis.