肠道微生物群在大豆皂甙预防蛋氨酸和胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎（NASH）小鼠肝脂肪变性中的预防生物活性中发挥重要作用。

Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet-Induced Non-Alcoholic Steatohepatitis (NASH) Mice.

机构信息

Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA), Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China.

Department of Clinical Nutrition, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510280, P. R. China.

出版信息

Mol Nutr Food Res. 2024 Feb;68(4):e2300561. doi: 10.1002/mnfr.202300561. Epub 2024 Jan 17.

DOI:10.1002/mnfr.202300561

PMID:38234006

Abstract

SCOPE

Gut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS-A and SS-Bb) against NASH and explores the mechanisms by targeting GM.

METHODS AND RESULTS

Male C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS-A , SS-Bb, or not for 16 weeks. Antibiotics-treated pseudo germ-free (PGF) mice are fed with MCD diet containing SS-A , SS-Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC-MS/MS. In NASH mice, SS-A and SS-Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF-α, IL-6, α-SMA, triglycerides, and cholesterol in liver. SS-A and SS-Bb decrease Firmicutes, Erysipelotrichaceae, unidentified-Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS-A and SS-Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO-1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS-A and SS-Bb against NASH.

CONCLUSION

GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet-induced NASH mice.

摘要

范围

肠道微生物群（GM）参与非酒精性脂肪性肝炎（NASH）的发展。植物化学物质大豆皂素有预防 NASH 的作用，可能通过调节 GM 来实现。本研究旨在研究大豆皂素单体（SS-A 和 SS-Bb）对 NASH 的预防作用，并探讨针对 GM 的机制。

方法和结果

雄性 C57BL/6 小鼠用含 SS-A、SS-Bb 或不含 SS-A、SS-Bb 的蛋氨酸和胆碱缺乏（MCD）饮食喂养 16 周。抗生素处理的假无菌（PGF）小鼠用含 SS-A、SS-Bb 或不含 SS-A、SS-Bb 的 MCD 饮食喂养 8 周。通过 16S rRNA 扩增子测序测定 GM。通过 UPLC-MS/MS 测定胆汁酸（BAs）。在 NASH 小鼠中，SS-A 和 SS-Bb 可缓解肝脂肪变性和纤维化，降低血清 ALT、AST 和 LPS，降低肝脏 TNF-α、IL-6、α-SMA、甘油三酯和胆固醇。SS-A 和 SS-Bb 降低厚壁菌门、Erysipelotrichaceae、未鉴定-Clostridiales、Eggerthellaceae、Atopobiaceae、Aerococcus、Jeotgalicoccus、Gemella、Rikenella，增加变形菌门、Verrucomicrobia、Akkermansiaceae、Romboutsia 和 Roseburia。SS-A 和 SS-Bb 改变肝脏、血清和粪便中的 BAs 组成，激活肝脏和回肠中的法尼醇 X 受体（FXR），增加肠道中的紧密连接蛋白和 ZO-1。然而，GM 清除会破坏 SS-A 和 SS-Bb 对 NASH 的预防作用。