Desynchrony of the mammalian circadian clock has known detrimental metabolic effects, but how synchronous and desynchronous signals are transmitted is unclear. A new study reports that the hepatic vagal afferent nerve (HVAN) transmits signals to the brain that result in changes in food intake and that ablation of the HVAN can prevent aberrant food intake. “We previously reported defects in the molecular

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.

A new study published in Nature explores the dynamic changes that colorectal cancer (CRC) cells undergo during their transition to the metastatic state by comparing primary tumours with metastases. “Clinically, metastases are less responsive to therapy than primary tumours in the same patients, despite harbouring the same mutations,” says Karuna Ganesh, co-corresponding author of the study. The researchers

New research published in Science Translational Medicine identifies an interplay between tumour-intrinsic and tumour-extrinsic factors that drive resistance to treatment in pancreatic ductal adenocarcinoma (PDAC). The findings provide the rationale for combined therapies that target both oncogenic signalling and the tumour microenvironment to overcome PDAC drug resistance. Inhibitors of the RAS–MAPK

To define the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD) and identify therapeutic options, it is crucial to understand the sources of hepatic fat accumulation. In patients with MASLD, it is estimated that hepatic triglycerides are primarily derived from adipose tissue as free fatty acids (~59%), followed by de novo lipogenesis (~26%) and diet (~15%). However

To mark the twentieth anniversary of Nature Reviews Gastroenterology & Hepatology, we asked three experts to comment on how the gut microbiome has transformed our understanding of biology and the strengths and limitations of microbiome research today as well as to look ahead at what the next 20 years of microbiome research and clinical applications might look like. In this Viewpoint, Maria Carmen Collado

Subsets of human tuft cells retain their proliferative capacity throughout life and can act as a damage-induced pool of regenerative stem cells, report Huang et al. in Nature. Organoids containing all human intestinal cell types were generated by the researchers from a single mature proliferating human tuft cell. Organoids engineered to lack tuft cells did not regenerate after irradiation, unlike those

Consumption of no and low-alcohol (NoLo) beverages is now commonplace in modern society. However, the debate surrounding the relative risks and benefits of these products is nuanced and evolving, particularly in patients with a history of alcohol use disorder or alcohol-related liver disease. This Comment summarizes the major individual and public health implications of NoLo drinks in order to help

Twenty years since the launch of Nature Reviews Gastroenterology & Hepatology, developments in research and clinical practice continue apace. In our anniversary issue, we focus on the past, present and future of gastroenterology and hepatology.

From 12–15 October, United European Gastroenterology (UEG) Week was held in person in Vienna, Austria, and online simultaneously. According to the organizers, there were 11,377 total registrants from 114 countries or territories, of whom 11% were registered for the virtual congress, with 4,701 individuals registered for the Postgraduate Teaching Programme, of whom 19% were registered for virtual attendance

Apical sodium-dependent bile acid transporter inhibitors have revolutionized care for children with genetic cholestasis. This Clinical Outlook discusses how this new class of drugs came into clinical practice and how they might benefit transplant-free survival for a multitude of indications.

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-00981-6, published online 2 October 2024.

A phase IIIa trial tested the safety and efficacy of liraglutide, a glucagon-like peptide 1 receptor agonist, in 82 children (6 to <12 years) with obesity. The children were randomly assigned (2:1) to receive a daily dose of 3 mg liraglutide (or the maximum tolerated dose) or placebo and follow lifestyle interventions. The treatment lasted 56 weeks with a 26-week follow-up. In week 56, the primary

A multicentre, open-label, prospective, randomized controlled trial (TransMet) assessed liver transplantation plus chemotherapy in 94 patients (intention-to-treat population) with permanently unresectable colorectal liver metastases from resected BRAF-non-mutated colorectal cancer and with no extrahepatic disease. The trial took place in 20 tertiary centres in Europe between 2016 and 2021. Patients

We thank Avades and colleagues for the opportunity to expand on our expert panel consensus statement (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. Nat. Rev. Gastroenterol. Hepatol. 21, 626–645 (2024))1 to highlight the important role of persons with lived experience of alcohol use disorder (AUD) and/or

We fully support the consensus statement on designing clinical trials to address alcohol use in people with alcohol-associated liver disease (ALD), which aims to standardize and improve the design of ALD trials (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. Nat. Rev. Gastroenterol. Hepatol. 21, 626–645 (2024))1

Management of anticoagulation in cirrhosis is challenging because of the concomitant risk of both thromboembolism and bleeding complications. Randomized controlled studies are lacking. Direct oral anticoagulants seem to be the most manageable option. However, for patients with Child C cirrhosis, the only safer anticoagulant strategy, currently, is low-molecular-weight heparin.

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-00974-5, published online 5 September 2024.

To coincide with the 20th anniversary of Nature Reviews Gastroenterology & Hepatology, we asked three experts to reflect on the past, present and future of metabolic dysfunction-associated steatotic liver disease (MASLD) research and clinical management. They comment on how MASLD research and clinical management has changed over the past 20 years, the strengths and limitations of the MASLD field today

New research published in Nature Genetics shows how neoadjuvant chemotherapy and radiotherapy affect the tumour microenvironment (TME) in pancreatic ductal adenocarcinoma using single-cell spatial transcriptomics. To this end, the researchers developed a computational tool (namely, spatially constrained optimal transport interaction analysis (SCOTIA)) to map ligand–receptor interactions within the

Nature Reviews Gastroenterology & Hepatology is launching a new Series on justice, equity, diversity and inclusion in an effort to increase awareness and advance equitable health.

The food we eat includes complex microbiomes, but the diversity of these food microbiomes has not been explored fully. In a new study published in Cell, the microbial diversity of >2,500 food metagenomes has been assessed and analysed in connection with the human microbiome, generating a new open access resource, the curatedFoodMetagenomicData (cFMD). “We all knew how food microbes are important for

The current state of microbiome research in Africa can be leveraged to encourage the development and implementation of standardized processes for data collection and management. In this Comment, we provide some recommendations to enable the research community to fully harness the richness of the microbiome of African populations and potential opportunities therein.

Gastroenterology as a specialty can make a substantial contribution to reducing the carbon footprint of the health-care system. Concrete actions are needed to increase awareness, education and evidence-based knowledge on eco-sustainable diagnostic and therapeutic approaches to digestive diseases.

A study published in Nature elucidates the genomic landscape of colorectal cancer (CRC). Researchers performed whole-genome sequencing of CRC samples from participants in the UK 100,000 Genomes Project. Analysis of the samples (n = 2,023) identified >250 putative driver genes of CRC and characterized subgroups of CRC. For example, the researchers clustered microsatellite-stable CRC into four distinct

In a study published in Nature Medicine, researchers report an artificial intelligence (AI)-based digital pathology tool for scoring metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis (NASH)) histology. MASH clinical trial enrollment and endpoint assessment are based on histological criteria. The tool, which is termed AIM-MASH, produced predictions

New research has mapped neuroimmune interactions in the mouse gut, revealing that TRPV1-expressing nociceptor neurons (involved in visceral pain) control and suppress regulatory T (Treg) cells in the gut, increasing susceptibility to colitis in mouse models. The findings potentially link pain signalling with immunomodulatory mechanisms in the gut. In their screen, eight distinct neuronal subsets were

From 26–29 June 2024, Nature Reviews Gastroenterology & Hepatology attended the 56th meeting of the European Pancreatic Club (EPC) in Santiago de Compostela, Spain. The hybrid meeting featured sessions that traversed basic, translational and clinical science, with sessions dedicated to the latest research into acute and chronic pancreatitis, cystic pancreatic lesions and pancreatic cancer, among others

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-00955-8, published online 17 July 2024.