Data_Sheet_1_Saccharomyces Boulardii Ameliorates Non-alcoholic Steatohepatitis in Mice Induced by a Methionine-Choline-Deficient Diet Through Gut-Liver Axis.docx

Non-alcoholic steatohepatitis (NASH) is affecting people worldwide. Changes in the intestinal microbiome are crucial to NASH. A previous study showed that eradicating intestinal fungi ameliorates NASH; however, the role of intestinal fungi in the development of NASH remains unclear. Saccharomyces boulardii (SB), a dietary supplement yeast, has been reported to restore the integrity of the intestine. Here, we tested the effect of SB in the treatment of NASH. For this study, we fed eight-week-old C57/BL6 male mice either a methionine-choline deficient (MCD) diet or a normal chow diet (NCD) for eight weeks. Half of the MCD diet-fed mice were gavaged with SB (5 mg/day) once daily. The remainder of the NCD–fed mice were gavaged with normal saline as a control. The MCD diet-fed mice on SB supplement showed better liver function, less hepatic steatosis, and decreased inflammation. Both hepatic inflammatory gene expression and fibrogenic gene expression were suppressed in mice with SB gavage. Intestinal damage caused by the MCD diet was tampered with, intestine inflammation decreased, and gut permeability improved in mice that had been given the SB supplement. Deep sequencing of the fecal microbiome showed a potentially increased beneficial gut microbiota and increased microbiota diversity in the SB-supplemented mice. The SB supplement maintains gut integrity, increases microbial diversity, and increases the number of potentially beneficial gut microbiota. Thus, the SB supplement attenuates gut leakage and exerts a protective effect against NASH. Our results provide new insight into the prevention of NASH.

非酒精性脂肪性肝炎（Non-alcoholic steatohepatitis, NASH）是一种全球范围内高发的疾病。肠道微生物组的改变与NASH的发生发展密切相关。既往研究显示，清除肠道真菌可改善NASH，但肠道真菌在NASH病程中的具体作用仍未明确。布拉氏酵母菌（Saccharomyces boulardii, SB）作为一种膳食补充剂酵母，已有研究报道其可修复肠道黏膜完整性。本研究旨在探讨SB用于治疗NASH的效果。为此，我们将8周龄的C57/BL6雄性小鼠分为两组，分别饲喂甲硫氨酸-胆碱缺乏（Methionine-choline deficient, MCD）饲料与普通标准饲料（Normal chow diet, NCD），持续8周。其中，半数饲喂MCD饲料的小鼠每日灌胃布拉氏酵母菌（5 mg/天）一次，剩余饲喂普通标准饲料的小鼠则每日灌胃生理盐水作为对照。结果显示，补充SB的MCD饲料饲喂小鼠，其肝功能更佳、肝脂肪变性程度更轻、炎症水平更低。灌胃SB可抑制小鼠肝脏炎症基因与纤维化相关基因的表达。同时，MCD饲料诱导的肠道损伤得到改善，小鼠肠道炎症减轻、肠通透性提升。粪便微生物组深度测序结果表明，补充SB的小鼠肠道内潜在有益菌丰度与微生物多样性均有所升高。综上，布拉氏酵母菌补充剂可维持肠道黏膜完整性、提升微生物多样性，并增加潜在有益肠道菌群的数量，进而减轻肠道渗漏，对NASH发挥保护作用。本研究结果为NASH的预防提供了新的研究思路。