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膳食晚期糖基化终产物与肠道上皮的相互作用:我们究竟了解多少?

Dietary Advanced Glycation End products interacting with the intestinal epithelium: What do we really know?

机构信息

Department of Food Quality and Design, Wageningen University and Research, Bornse Weilanden 9, 6708 WG, Wageningen, the Netherlands.

Department of Food Quality and Design, Wageningen University and Research, Bornse Weilanden 9, 6708 WG, Wageningen, the Netherlands.

出版信息

Mol Metab. 2023 Jul;73:101734. doi: 10.1016/j.molmet.2023.101734. Epub 2023 Apr 29.

Abstract

BACKGROUND

Advanced Glycation End products (AGEs) are a heterogeneous group of stable reaction products formed when amino acids, peptides, or proteins are glycated by the non-enzymatic Maillard Reaction. The formation and accumulation of these products in vivo are linked to many inflammation-based pathological outcomes and part of the pathophysiology of non-communicable diseases like eye cataracts and Alzheimer's disease. Since our diet contains high levels of the same compounds, it has been questioned whether their consumption is also detrimental to health. However, this is still under debate. In this context, the intestinal epithelium is an important target tissue since it is chronically exposed to relatively high concentrations of dietary AGEs.

SCOPE OF REVIEW

This review summarizes the current evidence on the impact of dietary AGEs on the intestinal epithelium and critically reflects on its methodology.

MAJOR CONCLUSIONS

In healthy rodent models, an inflammation-independent impaired intestinal barrier function is claimed; however, dietary AGEs showed anti-inflammatory activity in IBD models. In vitro studies could be a valuable tool to unravel the underlying mechanisms of these effects, however the available studies face some limitations, e.g. lack of the physicochemical characterization of the glycated proteins, the inclusion of the proper controls and the dose-dependency of the effect. In addition, studies using more advanced in vitro models like intestinal organoids and co-cultures with immune cells exposed to gut microbial metabolites derived from the fermentation of AGEs are still needed.

摘要

背景

晚期糖基化终产物(AGEs)是由非酶促美拉德反应使氨基酸、肽或蛋白质糖化而形成的一组稳定的反应产物。这些产物在体内的形成和积累与许多基于炎症的病理结果有关,也是白内障和阿尔茨海默病等非传染性疾病的部分病理生理学基础。由于我们的饮食中含有高水平的相同化合物,因此有人质疑它们的摄入是否也对健康有害。然而,这仍然存在争议。在这种情况下,肠道上皮是一个重要的靶组织,因为它会长期暴露于相对较高浓度的膳食 AGEs 中。

综述范围

本文总结了关于膳食 AGEs 对肠道上皮影响的现有证据,并对其方法进行了批判性反思。

主要结论

在健康的啮齿动物模型中,据称会出现与炎症无关的肠道屏障功能受损;然而,在 IBD 模型中,膳食 AGEs 表现出抗炎活性。体外研究可能是揭示这些影响潜在机制的有价值工具,然而,现有研究存在一些局限性,例如缺乏糖化蛋白的理化特性描述、适当对照的纳入以及效应的剂量依赖性。此外,还需要使用更先进的体外模型,如肠道类器官和与肠道微生物代谢物共培养的免疫细胞,这些代谢物是由 AGEs 发酵产生的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5423/10197094/d0d10b7638d3/gr1.jpg

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