Orally Administered Natural Lipid Nanoparticle-Loaded 6-Shogaol Shapes the Anti-Inflammatory Microbiota and Metabolome.
Orally Administered Natural Lipid Nanoparticle-Loaded 6-Shogaol Shapes the Anti-Inflammatory Microbiota and Metabolome.
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DOI：
10.3390/pharmaceutics13091355
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发表时间：
2021-08-28
期刊：
影响因子：
5.4
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Yang C;Long D;Sung J;Alghoul Z;Merlin D
在过去的十年中，人们对微生物群靶向治疗策略越来越感兴趣，这些治疗策略旨在调节肠道微生物群的组成和/或功能，以治疗慢性疾病，如炎症性肠病（IBD）、代谢症状和肥胖症。虽然靶向肠道微生物群是治疗IBD的一种创新手段，但它通常需要延长治疗时间，阻碍了其潜在的应用。在本文中，使用已建立的天然脂质纳米颗粒（nLNP）平台，我们证明了用候选药物6-姜烯酚（6S/nLNP）包封的nLNP在治疗的一天内明显改变了微生物群组成，显著加速了使用游离6-姜烯酚（6S）通常需要五天的过程。此外，用6S/nLNP处理5天诱导的微生物群组成的变化维持至少15天（从第5天到第20天）。由该组成变化引起的粪便代谢谱的随后改变表现为功能变化，其分别增强了巨噬细胞（Raw 264.7）和上皮细胞（Caco-2 BBE 1）的体外抗炎和伤口愈合功效。此外，这种代谢组成的变化，反映在改变的代谢概况，促进了强大的抗炎作用，在DSS诱导的小鼠模型的急性结肠炎。我们的研究表明，通过几乎立即调节微生物群的组成和功能，基于nLNP的药物递送平台可能是治疗溃疡性结肠炎的有力工具。
The past decade has seen increasing interest in microbiota-targeting therapeutic strategies that aim to modulate the gut microbiota’s composition and/or function to treat chronic diseases, such as inflammatory bowel disease (IBD), metabolic symptoms, and obesity. While targeting the gut microbiota is an innovative means for treating IBD, it typically requires an extended treatment time, hampering its potential application. Herein, using an established natural-lipid nanoparticle (nLNP) platform, we demonstrate that nLNPs encapsulated with the drug candidate 6-shogaol (6S/nLNP) distinctly altered microbiota composition within one day of treatment, significantly accelerating a process that usually requires five days using free 6-shogaol (6S). In addition, the change in the composition of the microbiota induced by five-day treatment with 6S/nLNP was maintained for at least 15 days (from day five to day 20). The consequent alteration in the fecal metabolic profile stemming from this compositional change manifested as functional changes that enhanced the in vitro anti-inflammatory and wound-healing efficacy of macrophage cells (Raw 264.7) and epithelial cells (Caco-2 BBE1), respectively. Further, this metabolic compositional change, as reflected in an altered metabolic profile, promoted a robust anti-inflammatory effect in a DSS-induced mouse model of acute colitis. Our study demonstrates that, by near-instantly modulating microbiota composition and function, an nLNP-based drug-delivery platform might be a powerful tool for treating ulcerative colitis.
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影响因子：
5.9
作者：
Brown DG;Rao S;Weir TL;O'Malia J;Bazan M;Brown RJ;Ryan EP
通讯作者：
Ryan EP
DOI：
10.3390/ph14060571
发表时间：
2021-06-15
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Bischoff-Kont I;Fürst R
通讯作者：
Fürst R
DOI：
10.1007/s00018-017-2693-8
发表时间：
2018-01
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Hugenholtz F;de Vos WM
通讯作者：
de Vos WM
影响因子：
30.3
作者：
Teng, Yun;Ren, Yi;Zhang, Huang-Ge
通讯作者：
Zhang, Huang-Ge
影响因子：
0.8
作者：
Merlin-Zhang, Olivier;Sung, Junsik;Viennois, Emilie
通讯作者：
Viennois, Emilie