Metabolic dysfunction-associated steatotic liver disease, and the broader spectrum of steatotic liver disease (SLD), require tailored lifestyle interventions across different age groups, considering genetics, family invo...Metabolic dysfunction-associated steatotic liver disease, and the broader spectrum of steatotic liver disease (SLD), require tailored lifestyle interventions across different age groups, considering genetics, family involvement, and psychological, environmental and social factors. Clinical practice guidelines for adults typically recommend a uniform treatment approach, regardless of age-related considerations. However, different emphases might be needed for pregnant women, adults and the older age group (≥65 years of age). Moreover, metabolic health, and therefore liver health, are determined at a very early age and even in utero and infancy. Thus, the prevention and treatment of SLD should not be overlooked at these early life stages and should be specific for each stage of life. The life course approach is a comprehensive strategy that considers health needs across all stages of life, from infancy to older age. This Review puts the spotlight on these topics, creating a comprehensive age-chronological order overview of the literature, addressing gaps in knowledge, providing practical advice and highlighting age-related considerations, in contrast to a one-size-fits-all (ages) approach.
Autoimmune gastritis (AIG) is an immune-mediated condition that affects the oxyntic mucosa of the stomach, leading to progressive atrophy and deficiencies in vitamin B, iron and other micronutrients. Our understanding of...Autoimmune gastritis (AIG) is an immune-mediated condition that affects the oxyntic mucosa of the stomach, leading to progressive atrophy and deficiencies in vitamin B, iron and other micronutrients. Our understanding of the pathogenesis, clinical manifestations and management of AIG has improved in the past 20 years. Initially thought to be associated mainly with pernicious anaemia and limited to certain geographical areas, AIG is now recognized as a global disorder with a broad clinical spectrum, ranging from asymptomatic cases to gastrointestinal, haematological, neurological and gynaecological manifestations. The role of Helicobacter pylori in the development of AIG has been debated, with evidence suggesting that AIG might arise through distinct pathogenic pathways both related and unrelated to H. pylori infection. The risk of gastric adenocarcinoma in AIG has also been reassessed on the basis of studies exploring its natural history. Finally, novel insights have emerged regarding the characterization of 'potential AIG' and 'seronegative AIG', two distinct conditions that were previously overlooked. In this Review, we discuss the latest advances in the field of AIG.
The microbiome is widely involved in host metabolism, with many omics studies suggesting that it is important for metabolic health. Although studies in this area have made great strides in furthering our understanding of...The microbiome is widely involved in host metabolism, with many omics studies suggesting that it is important for metabolic health. Although studies in this area have made great strides in furthering our understanding of the role of the microbiome in health and disease, key challenges still hinder the safe clinical application of gut microbiota-targeted therapies. These limitations include a lack of confirmation of causality between the gut microbiota and host health, insights into the molecular mechanisms by which the gut microbiota functions to affect host health, and the development of therapeutic strategies that accurately regulate the function of the gut microbiota towards specific microbial enzyme targets without affecting its overall composition and viability. Microbial enzymes with various functions and activities have attracted the attention of many researchers in the past few years, especially microbiota-host isozymes, which are enzymes in the microbiome and the host that share a similar function. Such isozymes, as well as microbial-specific enzymes involved in basic biological processes of the gut microbiota, metabolism of nutrients, and synthesis of active metabolites and interactions in microbial-host communities, are the key mediators of gut microbiota-host crosstalk and have received much attention. In this Review, we provide a holistic understanding of the multifaceted role of gut microbial enzymes, including providing guidance for their discovery, while highlighting the great potential of gut microbial enzyme-oriented therapies for precision medicine.
Human liver tissue has been found to contain microplastics and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has markedly increased over the past 10 years, prompting critical questions regarding their...Human liver tissue has been found to contain microplastics and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has markedly increased over the past 10 years, prompting critical questions regarding their potential causal role in liver disease. In cell-based and murine models, MNP exposure can trigger oxidative stress, fibrogenesis and inflammation, pathological features that resemble those of advanced liver disease, suggesting shared mechanistic pathways. Furthermore, the capacity for MNPs to act as vectors for microbial pathogens, antimicrobial resistance, endocrine-disrupting chemicals and carcinogenic additives might have important implications for liver pathology. This Perspective examines emerging evidence on the consequences of MNPs for liver health and disease, introducing the concept of plastic-induced liver injury. By highlighting critical methodological bottlenecks, key knowledge gaps and unmet research priorities, it lays out a road map for the emerging field of environmental hepatology.
Colitis-associated colorectal cancer (caCRC) is a subset of lower gastrointestinal tract malignancies that occurs in patients with inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. The glo...Colitis-associated colorectal cancer (caCRC) is a subset of lower gastrointestinal tract malignancies that occurs in patients with inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. The global prevalence of IBD is increasing, putting more individuals at risk of developing caCRC. The pathophysiological mechanisms that underlie the initiation and growth of caCRC remain to be fully elucidated. Nevertheless, studies have provided novel insights into the pathophysiology of caCRC, underscoring the distinguishing characteristics of caCRC compared with sporadic forms of CRC. In this Review, we describe the key mechanisms that drive caCRC. Starting from a clinical perspective and highlighting key features of the tumour epithelium, we discuss typical caCRC-related characteristics among subtypes of CRC, with a particular focus on the role of stromal cells in the tumour microenvironment. In addition, we review the contributions of immune cells to tumour control versus tumour promotion, and how signals from the gut microbiome might influence tumour development in caCRC. We also discuss various aspects of the pathophysiological heterogeneity of caCRC. Finally, we outline potential implications for therapy, and how these findings could be translated into future strategies of personalized medicine targeting caCRC.
Artificial intelligence (AI) is rapidly transforming the management landscape of inflammatory bowel disease (IBD). While early applications in endoscopy, digital pathology and cross-sectional imaging drew substantial att...Artificial intelligence (AI) is rapidly transforming the management landscape of inflammatory bowel disease (IBD). While early applications in endoscopy, digital pathology and cross-sectional imaging drew substantial attention, next-generation AI systems that enable deeper disease understanding, personalized treatment and streamlined clinical workflows are now emerging. These advances encompass the multimodal integration of endoscopic, histological and molecular data ('endo-histo-omics'); AI-assisted assessment of the intestinal barrier; remote monitoring via wearables; and the incorporation of large language models for decision-making support and patient interactions. This Perspective traces the evolution of AI in IBD from domain-specific tools to foundational platforms supporting data-driven precision medicine. We highlight validated AI applications across diagnosis, monitoring, outcome prediction and neoplasia surveillance. We also explore the expectations of key stakeholders, including clinicians, patients, regulatory bodies and industry, and discuss unresolved challenges such as explainability, integration into workflows, reimbursement and environmental sustainability. By aligning innovation with ethical and clinical priorities, AI holds the potential to redefine IBD care. Its future will be shaped by collaboration, transparency and responsible implementation, ushering in a new era of personalized, efficient and equitable care for individuals with IBD.
Metabolic dysfunction-associated steatotic liver disease (MASLD), a leading global cause of chronic liver disease, encompasses a wide spectrum of disease stages from isolated hepatic steatosis to cirrhosis. After decades...Metabolic dysfunction-associated steatotic liver disease (MASLD), a leading global cause of chronic liver disease, encompasses a wide spectrum of disease stages from isolated hepatic steatosis to cirrhosis. After decades of limited therapeutic options, pivotal developments, including the landmark FDA conditional approvals of resmetirom and semaglutide, mark a transformative era for metabolic dysfunction-associated steatohepatitis (MASH) management, with numerous additional promising treatments rapidly advancing through late-stage development. These milestones validate targeting both upstream metabolic dysfunction and intrahepatic injury, catalysing interest in rational combination strategies tailored to patient phenotype and disease stage. However, major challenges persist: the absence of dynamic, validated biomarkers of response; ongoing reliance on biopsy-based surrogates; high placebo response rates; and heterogeneity in disease biology and clinical course. Emerging approaches, such as noninvasive tests and multi-omic profiling, promise to refine patient selection, enrich trials and enable longitudinal monitoring at scale. This Review synthesizes lessons learned from prior trials and critically appraises current and emerging drug classes. We propose a pragmatic, mechanism-aligned framework for personalized MASH care that integrates lifestyle intervention, incretin-based therapies and liver-directed agents, with the overarching objective of mitigating progression to liver-related complications while simultaneously addressing the excess cardiometabolic morbidity and mortality that characterize this multisystem disorder.