miRNA-21影响小肠菌群以促进小鼠肝损伤
创作:szx 审核:szx 2020年12月25日
  • 在胆管结扎(BDL)诱导的肝损伤小鼠模型中,miRNA-21的缺失可减少肝脏及小肠的损伤,并恢复小肠菌群的失调;
  • 在miRNA-21敲除小鼠的小肠菌群中,乳杆菌属的丰度显著增加;
  • 在体外,miRNA-21可显著抑制2种罗伊氏乳杆菌菌株的生长;
  • 在BDL小鼠中,补充罗伊氏乳杆菌DSM 17938,可模拟miRNA-21缺失对肝损伤的保护作用;
  • 乳杆菌属可能通过产生D-乳酸盐,以降低巨噬细胞的TGF-β表达,从而抑制BDL诱导的肝损伤。
主编推荐语
szx
先前研究发现,敲除miRNA-21可在胆汁淤积性肝损伤中起到保护性作用。Gut Microbes上发表的一项最新研究,发现敲除miRNA-21可增加胆汁淤积性肝损伤小鼠模型的小肠菌群中的乳杆菌属丰度,而补充罗伊氏乳杆菌菌株可模拟敲除miRNA-21对小鼠肝损伤的保护性作用。
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Gut Microbes [IF:7.74]

Host miRNA-21 promotes liver dysfunction by targeting small intestinal Lactobacillus in mice

宿主miRNA-21通过靶向小肠乳杆菌属促进小鼠的肝功能失调

10.1080/19490976.2020.1840766

2020-12-10, Article

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New evidence shows that host-microbiota crosstalk can be modulated via endogenous miRNAs. We have previously reported that miR-21 ablation protects against liver injury in cholestasis. In this study, we investigated the role of miR-21 in modulating the gut microbiota during cholestasis and its effects in liver dysfunction. Mice lacking miR-21 had reduced liver damage and were protected against small intestinal injury as well as from gut microbiota dysbiosis when subjected to bile duct ligation surgery. The unique microbiota profile of miR-21KO mice was characterized by an increase in Lactobacillus, a key microbiome genus for gut homeostasis. Interestingly, in vitro incubation of synthetic miR-21 directly reduced Lactobacillus load. Moreover, supplementation with Lactobacillus reuteri revealed reduced liver fibrosis in acute bile duct-ligated mice, mimicking the protective effects in miR-21 knockout mice. D-lactate, a main product of Lactobacillus, regulates gut homeostasis that may link with reduced liver fibrosis. Altogether, our results demonstrate that miR-21 promotes liver dysfunction through direct modulation of the gut microbiota and highlight the potential therapeutic effects of Lactobacillus supplementation in gut and liver homeostasis.

First Authors:
André A Santos

Correspondence Authors:
André A Santos,Cecília MP Rodrigues

All Authors:
André A Santos,Marta B Afonso,Ricardo S Ramiro,David Pires,Madalena Pimentel,Rui E Castro,Cecília MP Rodrigues

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