State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, China.
Biomed Pharmacother. 2021 Jan;133:111000. doi: 10.1016/j.biopha.2020.111000. Epub 2020 Nov 14.
Liver failure is a serious hepatic dysfunction with high mortality. This work aimed to investigate the effect of a famous probiotic and drug, Lactobacillus reuteri DSM 17938, on liver failure in rats. Sprague-Dawley rats were gavaged with 3 × 10 CFU of DSM 17938 for 7 days. d-galactosamine was intraperitoneally injected to induce acute liver failure on the eighth day. Samples were collected to determine the liver function, serum cytokines levels, terminal ileum and liver histology, gut microbiota, metabolome and transcriptome. Our results showed that pretreatment with DSM 17938 not only reduced the elevation in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, IL-1α, IL-2, IL-18, M-CSF, and MIP-3α levels but also alleviated histological abnormalities of both the terminal ileum and liver induced by d-galactosamine. Additionally, DSM 17938 reduced d-galactosamine-induced enrichment of some taxa of gut Actinobacteria or Firmicutes, including abundant pathogens such as Actinomycetales, Coriobacteriaceae, Staphylococcaceae and Enterococcaceae. Furthermore, DSM 17938 reduced the d-galactosamine-induced increase in not only fecal metabolites such as trisaminol and lithocholic acid but also the transcription of liver inflammatory genes, such as Ccl2, Ccl7, Ccl11, Ccl12, Il6, Il11, Il20rb, Mmp3 and Mmp10. Downregulation of retinol metabolism and PPAR signaling pathway as well as upregulation of viral protein interaction with cytokine and cytokine receptor and central carbon metabolism in cancer signaling pathway were involved in the mechanism of L. reuteri DSM 17938 alleviating liver failure. Our findings suggested that DSM 17938 is a potential probiotic for the prevention or treatment of liver failure.
肝衰竭是一种严重的肝功能障碍，死亡率很高。本研究旨在探讨一种著名的益生菌和药物，鼠李糖乳杆菌 DSM 17938，对大鼠肝衰竭的影响。Sprague-Dawley 大鼠连续 7 天灌胃 3×10 CFU DSM 17938，第 8 天腹腔注射半乳糖胺诱导急性肝衰竭。收集样本以测定肝功能、血清细胞因子水平、末端回肠和肝脏组织学、肠道微生物群、代谢组和转录组。我们的结果表明，DSM 17938 预处理不仅降低了血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-谷氨酰转移酶、IL-1α、IL-2、IL-18、M-CSF 和 MIP-3α 水平的升高，还减轻了半乳糖胺引起的末端回肠和肝脏组织学异常。此外，DSM 17938 减少了半乳糖胺诱导的某些肠道放线菌或厚壁菌门的富集，包括丰度较高的病原体，如放线菌目、科里氏菌科、葡萄球菌科和肠球菌科。此外，DSM 17938 降低了不仅粪便代谢物如 trisaminol 和石胆酸的增加，还降低了肝脏炎症基因的转录，如 Ccl2、Ccl7、Ccl11、Ccl12、Il6、Il11、Il20rb、Mmp3 和 Mmp10。视黄醇代谢和 PPAR 信号通路的下调以及病毒蛋白与细胞因子和细胞因子受体相互作用以及癌症信号通路中的中央碳代谢的上调参与了鼠李糖乳杆菌 DSM 17938 缓解肝衰竭的机制。我们的研究结果表明，DSM 17938 是预防或治疗肝衰竭的潜在益生菌。
