Polyphenol Microbial Metabolites Exhibit Gut and Blood-Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation
Polyphenol Microbial Metabolites Exhibit Gut and Blood-Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation
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DOI：
10.3390/metabo9040078
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发表时间：
2019-04-01
期刊：
影响因子：
4.1
通讯作者：
Bertin, Matthew J.
中科院分区：
文献类型：
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作者：
Johnson, Shelby L.;Kirk, Riley D.;Bertin, Matthew J.
越来越多的证据支持富含多酚的饮食，包括传统的地中海饮食，对管理心血管疾病、肥胖和神经退行性疾病的有益效果。然而，在讨论富含多酚的饮食对疾病的保护作用时，一个共同的担忧是，这些化合物是否以其完整/亲本的形式存在于体内循环中，以便在体内发挥其有益的作用。在这里，我们探索了两种常见的饮食多酚，即异黄酮类和木脂素类，及其肠道微生物衍生的代谢物对肠道和血脑屏障预测的通透性，以及对小鼠BV-2小胶质细胞神经炎性刺激的保护作用。与母体化合物相比，多酚微生物代谢物(PMM)对人工肠道和血脑屏障的渗透性通常更强。评价了母体多酚及其相应的PMM对内毒素诱导的BV-2小胶质细胞炎症的保护作用。木脂素来源的PMM，木酚和肠内酯，显示出对BV-2小胶质细胞产生一氧化氮和促炎细胞因子(IL-6和TNF-)的保护作用。因此，PMM可能在很大程度上有助于多酚饮食的有益效果，进一步支持肠道微生物区系在人类健康和疾病预防中的重要作用。
Increasing evidence supports the beneficial effects of polyphenol-rich diets, including the traditional Mediterranean diet, for the management of cardiovascular disease, obesity and neurodegenerative diseases. However, a common concern when discussing the protective effects of polyphenol-rich diets against diseases is whether these compounds are present in systemic circulation in their intact/parent forms in order to exert their beneficial effects in vivo. Here, we explore two common classes of dietary polyphenols, namely isoflavones and lignans, and their gut microbial-derived metabolites for gut and blood-brain barrier predicted permeability, as well as protection against neuroinflammatory stimuli in murine BV-2 microglia. Polyphenol microbial metabolites (PMMs) generally showed greater permeability through artificial gut and blood-brain barriers compared to their parent compounds. The parent polyphenols and their corresponding PMMs were evaluated for protective effects against lipopolysaccharide-induced inflammation in BV-2 microglia. The lignan-derived PMMs, equol and enterolactone, exhibited protective effects against nitric oxide production, as well as against pro-inflammatory cytokines (IL-6 and TNF-) in BV-2 microglia. Therefore, PMMs may contribute, in large part, to the beneficial effects attributed to polyphenol-rich diets, further supporting the important role of gut microbiota in human health and disease prevention.