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硫酸葡聚糖钠诱导的肠道微生物群失调加重了S100诱导的自身免疫性肝炎小鼠的肝损伤。

Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis.

作者信息

Wang Zi-Ying, Gao Ping-Ping, Li Ling, Chen Ting-Ting, Li Nan, Qi Meng, Zhang Sheng-Nan, Xu Ya-Ping, Wang Yu-Han, Zhang Shi-Hao, Zhang Ling-Ling, Wei Wei, Du Min, Sun Wu-Yi

机构信息

Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China.

Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230032, China.

出版信息

Immunol Lett. 2023 Nov;263:70-77. doi: 10.1016/j.imlet.2023.10.001. Epub 2023 Oct 4.

Abstract

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

摘要

近年来,自身免疫性肝炎(AIH)的发病率逐渐上升,若不治疗,该疾病最终可发展为肝硬化甚至肝癌。AIH患者常伴有肠道微生物群失调,但肠道微生物群失调是否会促进AIH的进展仍不清楚。在本研究中,我们研究了肠道微生物群失调在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠AIH发生发展中的作用。将C57BL/6J小鼠随机分为正常组、S100诱导的AIH组和DSS+S100组(饮用水中含1% DSS),实验周期持续4周。我们证明,给予DSS会加重肝脏炎症和肠道屏障破坏,并显著改变S100诱导的AIH小鼠肠道微生物群的组成,其主要特征是致病菌丰度增加,有益菌丰度降低。这些结果表明,给予DSS会加重S100诱导的AIH的肝损伤,这可能是由于DSS诱导的肠道微生物群失调,导致肠道屏障破坏,进而微生物易位至肝脏,加重肝脏炎症。

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