Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis
- 주제(기타) Chemistry, Physical
- 주제(기타) Materials Science, Multidisciplinary
- 주제(기타) Physics, Applied
- 주제(기타) Physics, Condensed Matter
- 설명문(일반) [Lee, Yonghyun; Moon, James J.] Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA; [Lee, Yonghyun; Moon, James J.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA; [Lee, Yonghyun; Moon, James J.] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA; [Sugihara, Kohei; Gillilland, Merritt G., III; Kamada, Nobuhiko] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA; [Jon, Sangyong] Korea Adv Inst Sci & Technol, KAIST Inst BioCentury, Dept Biol Sci, Daejeon, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000172065
- 본문언어 영어
- Published As https://dx.doi.org/10.1038/s41563-019-0462-9
초록/요약
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.
more