Nature Reviews Gastroenterology &Hepatology最新文献

The incidence of inflammatory bowel disease (IBD) has risen in the past decades and has emerged as a global health issue. IBD is characterized by chronic inflammation of the gastrointestinal tract. There is compelling evidence for the role of biological sex in IBD epidemiology, pathophysiology, disease progression, symptoms and extra-intestinal diseases. IBD disease course, management and therapies differ between men and women, yet there is a paucity of analysis of sex as a factor. This Review discusses the known influence of sex-linked genetic factors, hormones and hormone receptors in IBD incidence, prevalence, disease burden and clinical manifestation. Furthermore, we review the mechanisms underlying these sex-dependent effects on the dysregulation of gastrointestinal mucosal immunity (immune, epithelial barrier and microbiota) in IBD. To support the progressive inclusion of sex in the study of IBD, we summarize the current standard research methodology that should be implemented to investigate sex as a biological variable in IBD studies. Enhanced comprehension of the influence of sex in IBD pathophysiology will advance the development of targeted therapies and improve patient care.

Μetabolic dysfunction-associated steatotic liver disease (MASLD) comprises a heterogeneous condition in the presence of steatotic liver. There can be a hierarchy of metabolic risk factors contributing to the severity of metabolic dysfunction and, thereby, the associated risk of both liver and extrahepatic outcomes, but the precise ranking and combination of metabolic syndrome (MetS) traits that convey the highest risk of major adverse liver outcomes and extrahepatic disease complications remains uncertain. Insulin resistance, low-grade inflammation, atherogenic dyslipidaemia and hypertension are key to the mechanisms of liver and extrahepatic complications. The liver is pivotal in MetS progression as it regulates lipoprotein metabolism and secretes substances that affect insulin sensitivity and inflammation. MASLD affects the kidneys, heart and the vascular system, contributing to hypertension and oxidative stress. To address the global health burden of MASLD, intensified by obesity and type 2 diabetes mellitus epidemics, a holistic, multidisciplinary approach is essential. This approach should focus on both liver disease management and cardiometabolic risk factors. This Review examines the link between metabolic dysfunction and liver dysfunction and extrahepatic disease outcomes, the diverse mechanisms in MASLD due to metabolic dysfunction, and a comprehensive, personalized management model for patients with MASLD.

In a new study published in Science, researchers identify a mechanism in mice by which the nervous and immune systems interact to regulate blood glucose levels by controlling pancreatic glucagon secretion.

First, they observed that mice with no adaptive lymphocytes and innate lymphoid cells (ILCs) (Rag2^−/−Il2rg^−/−) had reduced blood glucose and glucagon levels during fasting. But this effect was not observed in mice that only lacked adaptive lymphocytes, which implicated ILCs in glucose regulation. Specifically, transplanting group 2 ILCs (ILC2s) into mice lacking lymphocytes increased fasting blood glucose levels and secretion of pancreatic glucagon, a hormone that regulates blood glucose levels. In vitro observations suggested that cytokines produced by pancreas-resident ILC2s increased secretion of glucagon by α-cells in the islets of Langerhans.

Correction to: Nature Reviews Gastroenterology & Hepatology https://doi.org/10.1038/s41575-024-01035-7, published online 31 January 2025.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician–patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.

Metabolic dysfunction-associated steatohepatitis (MASH) is known to increase the risk of hepatocellular carcinoma (HCC), yet also triggers hepatocyte senescence (a tumour-suppressive cell state). New research shows that the gluconeogenic enzyme fructose-1,6-bisphophatase (FBP1) serves as a key control point in the switch from MASH to HCC. “Since senescence describes a non-dividing cell state associated with tumor suppression I found the phenomenon of MASH-associated senescence paradoxical and became interested in solving this conundrum,” explains lead author Michael Karin.

More research is planned to further investigate the development of MASH and HCC and determine whether this process can be targeted therapeutically. “We plan to take this forward by studying how MASH-inducing diets cause hepatocyte DNA damage and whether the activation of TP53 and the upregulation of FBP1 account for selective insulin resistance, which frequently accompanies MASH. We are also interested in finding out whether switching DNA-damage-induced senescence to DNA-damage-induced cell death would result in the attenuation of HCC development.”