Nawrot Margaux, Peschard Simon, Lestavel Sophie, Staels Bart
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France.
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France.
Metabolism. 2021 Oct;123:154844. doi: 10.1016/j.metabol.2021.154844. Epub 2021 Aug 1.
Type 2 diabetes (T2D) and Non-Alcoholic Fatty Liver Disease (NAFLD) are pathologies whose prevalence continues to increase worldwide. Both diseases are precipitated by an excessive caloric intake, which promotes insulin resistance and fatty liver. The role of the intestine and its crosstalk with the liver in the development of these metabolic diseases is receiving increasing attention. Alterations in diet-intestinal microbiota interactions lead to the dysregulation of intestinal functions, resulting in altered metabolite and energy substrate production and increased intestinal permeability. Connected through the portal circulation, these changes in intestinal functions impact the liver and other metabolic organs, such as visceral adipose tissue, hence participating in the development of insulin resistance, and worsening T2D and NAFLD. Thus, targeting the intestine may be an efficient therapeutic approach to cure T2D and NAFLD. In this review, we will first introduce the signaling pathways linking T2D and NAFLD. Next, we will address the role of the gut-liver crosstalk in the development of T2D and NAFLD, with a particular focus on the gut microbiota and the molecular pathways behind the increased intestinal permeability and inflammation. Finally, we will summarize the therapeutic strategies which target the gut and its functions and are currently used or under development to treat T2D and NAFLD.
2型糖尿病（T2D）和非酒精性脂肪性肝病（NAFLD）是在全球范围内患病率持续上升的疾病。这两种疾病都是由热量摄入过多引发的，热量摄入过多会导致胰岛素抵抗和脂肪肝。肠道及其与肝脏之间的相互作用在这些代谢性疾病发生发展中的作用正受到越来越多的关注。饮食与肠道微生物群相互作用的改变会导致肠道功能失调，进而导致代谢产物和能量底物生成改变以及肠道通透性增加。通过门静脉循环相连，肠道功能的这些变化会影响肝脏和其他代谢器官，如内脏脂肪组织，从而参与胰岛素抵抗的发生发展，并使T2D和NAFLD病情恶化。因此，针对肠道可能是治愈T2D和NAFLD的一种有效治疗方法。在本综述中，我们将首先介绍连接T2D和NAFLD的信号通路。接下来，我们将探讨肠-肝相互作用在T2D和NAFLD发生发展中的作用，特别关注肠道微生物群以及肠道通透性增加和炎症背后的分子途径。最后，我们将总结目前正在使用或正在研发的针对肠道及其功能来治疗T2D和NAFLD的治疗策略。
