Yang Chunhua, Long Dingpei, Sung Junsik, Alghoul Zahra, Merlin Didier
Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Atlanta Veterans Affairs Medical Center, Decatur, GA 30302, USA.
Pharmaceutics. 2021 Aug 28;13(9):1355. doi: 10.3390/pharmaceutics13091355.
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.
在过去十年中，人们对以微生物群为靶点的治疗策略越来越感兴趣，这些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。虽然针对肠道微生物群是治疗IBD的一种创新方法，但它通常需要较长的治疗时间，这阻碍了其潜在应用。在此，我们使用已建立的天然脂质纳米颗粒（nLNP）平台，证明包裹有候选药物6-姜辣素（6S/nLNP）的nLNP在治疗一天内就能显著改变微生物群的组成，大大加速了通常使用游离6-姜辣素（6S）需要五天才能完成的过程。此外，用6S/nLNP进行五天治疗所诱导的微生物群组成变化至少维持了15天（从第五天到第二十天）。这种组成变化导致的粪便代谢谱改变表现为功能变化，分别增强了巨噬细胞（Raw 264.7）和上皮细胞（Caco-2 BBE1）的体外抗炎和伤口愈合功效。此外，这种代谢组成变化反映在代谢谱的改变上，在DSS诱导的急性结肠炎小鼠模型中促进了强大的抗炎作用。我们的研究表明，通过近乎即时地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。
