Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism

被引：34

作者：

Li, Dongping ^{[1
]}

Chen, Yu ^{[2
]}

Wan, Meijuan ^{[1
]}

Mei, Fengyi ^{[1
]}

Wang, Fangzhao ^{[1
]}

Gu, Peng ^{[1
]}

Zhang, Xianglong ^{[1
]}

Wei, Rongjuan ^{[1
]}

Zeng, Yunong ^{[1
]}

Zheng, Hanzhao ^{[1
]}

Chen, Bangguo ^{[1
]}

Xiong, Qingquan ^{[1
]}

Xue, Tao ^{[1
]}

Guan, Tianshan ^{[2
]}

Guo, Jiayin ^{[3
]}

Tian, Yuanxin ^{[3
]}

Zeng, Li-Yan ^{[4
]}

Liu, Zhanguo ^{[5
]}

Yuan, Hang ^{[6
]}

Yang, Ling ^{[6
]}

Liu, Hongbin ^{[7
]}

Dai, Lei ^{[7
]}

Yu, Yao ^{[8
]}

Qiu, Yifeng ^{[8
]}

Wu, Peng ^{[8
]}

Win, Sanda ^{[9
]}

Than, Tin Aung ^{[9
]}

Wei, Riqing ^{[10
]}

Schnabl, Bernd ^{[11
]}

Kaplowitz, Neil ^{[9
]}

Jiang, Yong ^{[1
]}

Ma, Qiang ^{[10
]}

Chen, Peng ^{[1
,5
]}

机构：

[1] Southern Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Guangdong Prov Key Lab Prote, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Affiliated Hosp 7, Dept Gastroenterol, Foshan 528244, Peoples R China

[3] Southern Med Univ, Sch Pharmaceut Sci, NMPA Key Lab Res & Evaluat Drug Metab, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China

[4] Zhongkai Univ Agr & Engn, Sch Chem & Chem Engn, Guangzhou 510225, Peoples R China

[5] Southern Med Univ, Zhujiang Hosp, Dept Crit Care Med, Guangzhou 510280, Peoples R China

[6] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Div Gastroenterol, Wuhan 430022, Peoples R China

[7] Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, CAS Key Lab Quantitat Engn Biol, Shenzhen 518055, Peoples R China

[8] Southern Med Univ, Nanfang Hosp, Dept Urol, Guangzhou 510515, Peoples R China

[9] Univ Southern Calif, Res Ctr Liver Dis, Div Gastrointestinal & Liver Dis, Dept Med,Keck Sch Med, Los Angeles, CA 90089 USA

[10] Southern Med Univ, Sch Lab Med & Biotechnol, Dept Biopharmaceut, Guangdong Prov Key Lab Immune Regulat & Immunother, Guangzhou 510515, Peoples R China

[11] Univ Calif San Diego, Dept Med, 9500 Gilman Dr,MC0063, La Jolla, CA USA

来源：

CELL HOST & MICROBE | 2024年 / 32卷 / 01期

基金：

中国国家自然科学基金;

关键词：

INDUCED HEPATOTOXICITY; BENZOQUINONE IMINE; FAILURE; TRANSPLANTATION; HYPOMAGNESEMIA; MANAGEMENT; PROTECTS; OUTCOMES; RISK;

D O I：

10.1016/j.chom.2023.11.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF

引用

页码：48 / +

页数：25

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