肠道微生物、饮食和遗传是代谢性肝病的驱动因素:概述精准医学影响的叙述性综述》。

IF 4.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Nutritional Biochemistry Pub Date : 2024-07-17 DOI:10.1016/j.jnutbio.2024.109704
Jake B. Hermanson , Samar A. Tolba , Evan A. Chrisler , Vanessa A. Leone
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引用次数: 0

摘要

代谢功能障碍相关性脂肪性肝病(MASLD)的发病率正在迅速上升,影响着全球三分之一以上的人口。代谢功能障碍相关性脂肪性肝炎(MASH)是代谢功能障碍相关性脂肪性肝病的晚期形式,有望成为肝移植的头号适应症。尽管有 400 多项临床试验正在进行中,但美国食品及药物管理局批准用于 MASH 的药物却很有限,目前只有一种药物(resmetirom)上市。这可能是由于疾病的病理生理学具有异质性,涉及高度个体化的遗传和环境因素之间的相互作用。鉴于遗传、营养和肠道微生物组已成为 MASLD 和 MASH 发病机制的动态促成因素,要应用精准医疗方法克服人际变异性,就需要深入了解遗传、营养和肠道微生物组之间的相互作用。在此,我们将单独讨论其中几个因素的关联和分子基础,并在基于患者的研究和临床前动物模型系统的背景下概述它们之间的相互作用。最后,我们强调了需要进一步研究的知识空白,以帮助成功实施精准医疗,预防和缓解 MASLD 和 MASH。
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Gut microbes, diet, and genetics as drivers of metabolic liver disease: a narrative review outlining implications for precision medicine

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing in prevalence, impacting over a third of the global population. The advanced form of MASLD, Metabolic dysfunction-associated steatohepatitis (MASH), is on track to become the number one indication for liver transplant. FDA-approved pharmacological agents are limited for MASH, despite over 400 ongoing clinical trials, with only a single drug (resmetirom) currently on the market. This is likely due to the heterogeneous nature of disease pathophysiology, which involves interactions between highly individualized genetic and environmental factors. To apply precision medicine approaches that overcome interpersonal variability, in-depth insights into interactions between genetics, nutrition, and the gut microbiome are needed, given that each have emerged as dynamic contributors to MASLD and MASH pathogenesis. Here, we discuss the associations and molecular underpinnings of several of these factors individually and outline their interactions in the context of both patient-based studies and preclinical animal model systems. Finally, we highlight gaps in knowledge that will require further investigation to aid in successfully implementing precision medicine to prevent and alleviate MASLD and MASH.

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来源期刊
Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry 医学-生化与分子生物学
CiteScore
9.50
自引率
3.60%
发文量
237
审稿时长
68 days
期刊介绍: Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.
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