Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis
Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis
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DOI：
10.1038/s41563-019-0462-9
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发表时间：
2020-01-01
期刊：
影响因子：
41.2
通讯作者：
Moon, James J.
中科院分区：
文献类型：
--
作者：
Lee, Yonghyun;Sugihara, Kohei;Moon, James J.
虽然传统的治疗炎症性肠病的方法主要集中在抑制过度活跃的免疫反应上，但如何在炎症性肠病中解决肠道屏障破坏、肠道共生微生物区系失调和黏膜免疫反应失调等问题仍不清楚。此外，免疫抑制剂会引起非靶点的全身副作用和并发症。在这里，我们报道了透明质酸-胆红素纳米药物(HABN)的发展，它聚集在炎症的结肠上皮细胞中，并在急性结肠炎小鼠模型中恢复上皮屏障。令人惊讶的是，HABN还调节肠道微生物区系，增加了总体丰富度和多样性，并显著增加了粘液阿克曼氏菌和XIVα梭菌的丰度，这两种微生物在肠道内稳态中起着关键作用。重要的是，HABN与促炎巨噬细胞相关，调节先天免疫反应，对结肠炎具有强大的治疗效果。我们的工作揭示了纳米疗法对肠道动态平衡、微生物群和先天免疫反应的影响，以治疗炎症性疾病。
While conventional approaches for inflammatory bowel diseases mainly focus on suppressing hyperactive immune responses, it remains unclear how to address disrupted intestinal barriers, dysbiosis of the gut commensal microbiota and dysregulated mucosal immune responses in inflammatory bowel diseases. Moreover, immunosuppressive agents can cause off-target systemic side effects and complications. Here, we report the development of hyaluronic acid-bilirubin nanomedicine (HABN) that accumulates in inflamed colonic epithelium and restores the epithelium barriers in a murine model of acute colitis. Surprisingly, HABN also modulates the gut microbiota, increasing the overall richness and diversity and markedly augmenting the abundance of Akkermansia muciniphila and Clostridium XIV alpha, which are microorganisms with crucial roles in gut homeostasis. Importantly, HABN associated with pro-inflammatory macrophages, regulated innate immune responses and exerted potent therapeutic efficacy against colitis. Our work sheds light on the impact of nanotherapeutics on gut homeostasis, microbiome and innate immune responses for the treatment of inflammatory diseases.