Nature Reviews Gastroenterology &Hepatology最新文献

PDAC: advances in tumour microenvironment, microbiome and AI

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-20 DOI: 10.1038/s41575-024-01030-y

Minoti Apte

引用次数: 0

Biologic agents for IBD come of age as host–microbe interactions emerge

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-13 DOI: 10.1038/s41575-024-01029-5

Leolin Katsidzira, Benjamin Misselwitz

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Antibiotic-perturbed microbiota and the role of probiotics

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-11 DOI: 10.1038/s41575-024-01023-x

Hania Szajewska, Karen P. Scott, Tim de Meij, Sofia K. Forslund-Startceva, Rob Knight, Omry Koren, Paul Little, Bradley C. Johnston, Jan Łukasik, Jotham Suez, Daniel J. Tancredi, Mary Ellen Sanders

{"title":"Antibiotic-perturbed microbiota and the role of probiotics","authors":"Hania Szajewska, Karen P. Scott, Tim de Meij, Sofia K. Forslund-Startceva, Rob Knight, Omry Koren, Paul Little, Bradley C. Johnston, Jan Łukasik, Jotham Suez, Daniel J. Tancredi, Mary Ellen Sanders","doi":"10.1038/s41575-024-01023-x","DOIUrl":"https://doi.org/10.1038/s41575-024-01023-x","url":null,"abstract":"The disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been advanced, with little consideration of the strength of evidence supporting it. Some clinical data suggest that probiotics can reduce antibiotic-related side effects, including Clostridioides difficile-associated diarrhoea, but there are no data that causally link these clinical effects to microbiota protection or recovery. Substantial challenges hinder attempts to address this hypothesis, including the absence of consensus on the composition of a ‘normal’ microbiota, non-standardized and evolving microbiome measurement methods, and substantial inter-individual microbiota variation. In this Review, we explore these complexities. First, we review the known benefits and risks of antibiotics, the effect of antibiotics on the human microbiota, the resilience and adaptability of the microbiota, and how microbiota restoration might be defined and measured. Subsequently, we explore the evidence for the efficacy of probiotics in preventing disruption or aiding microbiota recovery post-antibiotic treatment. Finally, we offer insights into the current state of research and suggest directions for future research.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"28 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Precision models in hepatocellular carcinoma

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-11 DOI: 10.1038/s41575-024-01024-w

Marina Barcena-Varela, Satdarshan P. Monga, Amaia Lujambio

{"title":"Precision models in hepatocellular carcinoma","authors":"Marina Barcena-Varela, Satdarshan P. Monga, Amaia Lujambio","doi":"10.1038/s41575-024-01024-w","DOIUrl":"https://doi.org/10.1038/s41575-024-01024-w","url":null,"abstract":"Hepatocellular carcinoma (HCC) represents a global health challenge, and ranks among one of the most prevalent and deadliest cancers worldwide. Therapeutic advances have expanded the treatment armamentarium for patients with advanced HCC, but obstacles remain. Precision oncology, which aims to match specific therapies to patients who have tumours with particular features, holds great promise. However, its implementation has been hindered by the existence of numerous ‘HCC influencers’ that contribute to the high inter-patient heterogeneity. HCC influencers include tumour-related characteristics, such as genetic alterations, immune infiltration, stromal composition and aetiology, and patient-specific factors, such as sex, age, germline variants and the microbiome. This Review delves into the intricate world of HCC, describing the most innovative model systems that can be harnessed to identify precision and/or personalized therapies. We provide examples of how different models have been used to nominate candidate biomarkers, their limitations and strategies to optimize such models. We also highlight the importance of reproducing distinct HCC influencers in a flexible and modular way, with the aim of dissecting their relative contribution to therapy response. Next-generation HCC models will pave the way for faster discovery of precision therapies for patients with advanced HCC.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune-mediated liver injury from checkpoint inhibitors: mechanisms, clinical characteristics and management

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-11 DOI: 10.1038/s41575-024-01019-7

Evangelos Triantafyllou, Cathrin L. C. Gudd, Lucia A. Possamai

引用次数: 0

Current and emerging strategies for the prevention of hepatocellular carcinoma

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-09 DOI: 10.1038/s41575-024-01021-z

Yee Hui Yeo, Manal Abdelmalek, Seema Khan, Cynthia A. Moylan, Luz Rodriquez, Augusto Villanueva, Ju Dong Yang

{"title":"Current and emerging strategies for the prevention of hepatocellular carcinoma","authors":"Yee Hui Yeo, Manal Abdelmalek, Seema Khan, Cynthia A. Moylan, Luz Rodriquez, Augusto Villanueva, Ju Dong Yang","doi":"10.1038/s41575-024-01021-z","DOIUrl":"https://doi.org/10.1038/s41575-024-01021-z","url":null,"abstract":"Liver cancer is the third leading cause of cancer-related deaths globally, with incident cases expected to rise from 905,700 in 2020 to 1.4 million by 2040. Hepatocellular carcinoma (HCC) accounts for about 80% of all primary liver cancers. Viral hepatitis and chronic excessive alcohol consumption are major risk factors for HCC, but metabolic dysfunction-associated steatotic liver disease is also becoming a dominant cause. The increasing numbers of cases of HCC and changes in risk factors highlight the urgent need for updated and targeted prevention strategies. Preventive interventions encompass strategies to decrease the burden of chronic liver diseases and their progression to HCC. These strategies include nutritional interventions and medications that have shown promise in preclinical models. Although prevailing approaches focus on treating chronic liver disease, leveraging a wider range of interventions represents a promising area to safeguard at-risk populations. In this Review, we explore existing evidence for preventive strategies by highlighting established and potential paths to reducing HCC risk effectively and safely, especially in individuals with chronic liver diseases. We categorize the preventive strategies by the mechanism of action, including anti-inflammatory, antihyperglycaemic, lipid-lowering, nutrition and dietary, antiviral, and antifibrotic pathways. For each category, we discuss the efficacy and safety information derived from mechanistic, translational, observational and clinical trial data, pinpointing knowledge gaps and directions for future research.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"226 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The steatotic liver disease burden paradox: unravelling the key role of alcohol

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-12-05 DOI: 10.1038/s41575-024-01022-y

Nikolaj Torp, Mads Israelsen, Aleksander Krag

{"title":"The steatotic liver disease burden paradox: unravelling the key role of alcohol","authors":"Nikolaj Torp, Mads Israelsen, Aleksander Krag","doi":"10.1038/s41575-024-01022-y","DOIUrl":"https://doi.org/10.1038/s41575-024-01022-y","url":null,"abstract":"The classification of steatotic liver disease (SLD) has evolved, incorporating all conditions characterized by hepatic lipid accumulation. SLD represents a continuum of disorders that are shaped by the dynamic factors of alcohol intake and cardiometabolic risk factors. This updated classification has profound implications for both the management and research of SLD, especially with the new distinct category of patients with both metabolic and alcohol-related liver disease. In this Perspective, we highlight the pivotal role of alcohol within the SLD framework. We introduce the ‘SLD burden paradox’: a concept illustrating the disparity in which metabolic dysfunction-associated steatotic liver disease is more prevalent, yet individuals with SLD and excessive alcohol intake (such as in metabolic and alcohol-related liver disease and in alcohol-related liver disease) account for greater global liver-related morbidity and mortality. We explore strategies to mitigate the effect of SLD on morbidity and mortality, emphasizing the importance of early detection and reducing stigma associated with alcohol intake. Our discussion extends to methods for assessing and monitoring alcohol intake together with the critical role of managing cardiometabolic risk factors in patients across the SLD spectrum. Conclusively, we advocate for a coordinated care framework that adopts a person-centric approach when managing SLD, aiming to improve outcomes and patient care.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"83 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatic vagus nerve relays signals to the brain that can alter food intake

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-11-29 DOI: 10.1038/s41575-024-01028-6

Rebecca Kelsey

引用次数: 0

Moving towards more personalized approaches in locally advanced and metastatic colorectal cancer 在局部晚期和转移性结直肠癌的治疗中采用更加个性化的方法

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-11-28 DOI: 10.1038/s41575-024-01025-9

Chelsie K. Sievers, Cathy Eng

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The ins and outs of tumour resistance 肿瘤抗药性的来龙去脉

IF 65.1 1区医学

Nature Reviews Gastroenterology &Hepatology Pub Date : 2024-11-22 DOI: 10.1038/s41575-024-01027-7

Michael Attwaters

{"title":"The ins and outs of tumour resistance","authors":"Michael Attwaters","doi":"10.1038/s41575-024-01027-7","DOIUrl":"https://doi.org/10.1038/s41575-024-01027-7","url":null,"abstract":"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 pathway hold great promise as a therapeutic strategy for PDAC. However, patients rapidly develop drug resistance, explained in part by upregulation of members of the receptor tyrosine kinase family. The researchers found that the combination of RAS–MAPK inhibitors with inhibitors of focal adhesion kinase (FAK) — a non-receptor tyrosine kinase — reduced tumour growth and increased survival in several mouse models of PDAC to a greater extent than either therapy alone. Single-cell RNA sequencing and cell culture experiments revealed that cancer-associated fibroblasts in the tumour microenvironment are activated by FAK and impair the downregulation of MYC by RAS–MAPK inhibition in PDAC cells, resulting in drug resistance. “This identifies cancer-associated fibroblasts as a novel therapeutic target for overcoming RAS pathway resistance,” explains author Gregory Beatty.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"19 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0