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岩藻聚糖硫酸酯通过拟杆菌属调控肠-肝轴改善小鼠的酒精性肝损伤。

Fucoidan ameliorates alcohol-induced liver injury in mice through Parabacteroides distasonis-mediated regulation of the gut-liver axis.

机构信息

School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, PR China.

School of Agronomy and Life Science, Shanxi Datong University, Datong 037009, PR China.

出版信息

Int J Biol Macromol. 2024 Nov;279(Pt 3):135309. doi: 10.1016/j.ijbiomac.2024.135309. Epub 2024 Sep 3.

DOI:10.1016/j.ijbiomac.2024.135309
PMID:39236962
Abstract

Polysaccharides can benefit the liver via modulation of the gut microbiota, but the exact mechanism is still unclear. This study demonstrated that the effect of Scytosiphon lomentaria fucoidan (SLF) on alcohol-induced liver injury can be closely related to the level of Parabacteroides distasonis (Pd) via in vivo and in vitro models. Further mice experiment showed that Pd alleviated liver injury and inflammation by suppressing the NF-κB/MAPK pathways and activating Nrf2 pathway. The underlying mechanism can be closely associated with modulation of the gut microbiota, particularly an increase in microbiota diversity and beneficial bacteria and a reduction in Proteobacteria. Targeted metabolomics indicated that Pd ameliorated alcohol-induced dysbiosis of microbiota metabolites profile, primarily affecting amino acid metabolism. Moreover, Pd reduced the level of total bile acids (BAs) and improved BAs profile, affecting the expression levels of BA-associated genes in the liver and ileum involved in BA synthesis, transport, and reabsorption. This study suggests that SLF can benefit alcohol-induced liver injury via P. distasonis-mediated regulation of the gut-liver axis.

摘要

多糖可以通过调节肠道微生物群来有益于肝脏,但确切的机制尚不清楚。本研究表明,龙须菜岩藻聚糖(SLF)对酒精性肝损伤的影响可能与体内和体外模型中的副拟杆菌(Pd)水平密切相关。进一步的小鼠实验表明,Pd 通过抑制 NF-κB/MAPK 通路和激活 Nrf2 通路来减轻肝损伤和炎症。其潜在机制与肠道微生物群的调节密切相关,特别是增加了微生物多样性和有益细菌,减少了变形菌门。靶向代谢组学表明,Pd 改善了酒精诱导的微生物群代谢物谱失调,主要影响氨基酸代谢。此外,Pd 降低了总胆汁酸(BAs)的水平并改善了 BAs 谱,影响了肝脏和回肠中涉及 BAs 合成、运输和重吸收的与 BAs 相关基因的表达水平。本研究表明,SLF 可以通过 P. distasonis 介导的肠-肝轴调节来有益于酒精性肝损伤。

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