Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.
Cell Host Microbe
; 32(1): 48-62.e9, 2024 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-38056458
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Falência Hepática Aguda
/
Acetaminofen
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article