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三氯生靶向肠道微生物组可改善高脂肪饮食喂养小鼠的肝脂肪变性。

Triclosan targeting of gut microbiome ameliorates hepatic steatosis in high fat diet-fed mice.

机构信息

Department of Environmental and Occupational Health, Sichuan University West China School of Public Health and West China Fourth Hospital, Chengdu, 610041, Sichuan, China.

出版信息

J Antibiot (Tokyo). 2022 Jun;75(6):341-353. doi: 10.1038/s41429-022-00522-w. Epub 2022 Apr 19.

Abstract

Antibiotic use provides a promising strategy for the treatment of non-alcoholic fatty liver disease (NAFLD) by regulating the gut microbiota composition. Triclosan, a widely used antibiotic, may improve gut microbiome dysbiosis associated with NAFLD through the suppression of pathogenic gram-negative bacteria. However, the effects of triclosan on gut microbiota and hepatic steatosis and have not been explored in NAFLD mouse model. In this study, C57BL/6J mice were fed with high fat diet (HFD) for continuous 20 weeks and treated with triclosan at 400 mg/kg/d for 8 weeks from week 13. We explored the effects of triclosan on hepatic lipid accumulation and gut microbiome in HFD-fed mice by histological examination and 16 S ribosomal RNA sequencing, respectively. Analysis on the composition of gut microbiota indicated that triclosan suppressed pathogenic gram-negative bacteria, including Helicobacter, Erysipelatoclostridium and Citrobacter, and increased the ratio of Bacteroidetes/Firmicutes in HFD-fed mice. Meanwhile, triclosan increased the relative abundance of beneficial gut microbiomes including Lactobacillus, Bifidobacterium and Lachnospiraceae, which protected against metabolic abnormality. The results of alpha-diversity and beta-diversity also showed the improvement of triclosan on bacterial diversity and richness in HFD-fed mice. Pathway analysis further confirmed that triclosan can regulate nutrient and energy metabolism through the elimination of deleterious bacteria. As a result, triclosan intervention significantly reduced lipid accumulation and alleviated hepatic steatosis in HFD-fed mice. In conclusion, our results suggest that triclosan can alleviate liver steatosis in HFD-fed mice by targeting the gut microbiome.

摘要

抗生素通过调节肠道微生物组成,为非酒精性脂肪性肝病(NAFLD)的治疗提供了一种有前景的策略。三氯生是一种广泛使用的抗生素,通过抑制致病性革兰氏阴性菌,可能改善与 NAFLD 相关的肠道微生物失调。然而,三氯生对肠道微生物群和肝脂肪变性的影响尚未在 NAFLD 小鼠模型中得到探索。在本研究中,C57BL/6J 小鼠连续 20 周给予高脂肪饮食(HFD),并从第 13 周开始每周给予三氯生 400mg/kg/d 连续 8 周。我们通过组织学检查和 16S 核糖体 RNA 测序分别研究了三氯生对 HFD 喂养小鼠肝脂质积累和肠道微生物群的影响。肠道微生物群组成分析表明,三氯生抑制了致病性革兰氏阴性菌,包括 Helicobacter、Erysipelatoclostridium 和 Citrobacter,并增加了 HFD 喂养小鼠中厚壁菌门/拟杆菌门的比例。同时,三氯生增加了有益肠道微生物群的相对丰度,包括乳杆菌、双歧杆菌和lachnospiraceae,这有助于预防代谢异常。α多样性和β多样性的结果也表明,三氯生改善了 HFD 喂养小鼠的细菌多样性和丰富度。途径分析进一步证实,三氯生可以通过消除有害细菌来调节营养和能量代谢。结果,三氯生干预显著减少了 HFD 喂养小鼠的脂质积累,缓解了肝脂肪变性。总之,我们的结果表明,三氯生通过靶向肠道微生物群可以减轻 HFD 喂养小鼠的肝脂肪变性。

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