Fecal microbiota transplantation improves hepatic fibro-inflammation via regulating oxidative stress in experimental NASH.
Dig Liver Dis
; 55(11): 1521-1532, 2023 11.
Article
en En
| MEDLINE
| ID: mdl-37380586
ABSTRACT
Nonalcoholic steatohepatitis (NASH) is associated with imbalance of gut microbiome, indicating participation of gut environment in hepatic health status. Therefore, modulating gut environment via fecal microbiota transplantation (FMT) is a promising therapeutic procedure for NASH patients. However, the effect and mechanism of the FMT remains largely unknown. Here, we investigated the gut-liver axis to understand the FMT-mediated hepatic improvement in NASH. Feces from specific pathogen free mice were infused allogeneically into gastrointestinal tract of mice fed with high fat, high cholesterol and fructose (HFHCF), resulting in suppressing hepatic pathogenic events, featured by decreasing inflammatory and fibrotic mediators. The FMT elevated NF-E2-related factor 2 (NRF2), a key transcription factor that regulates antioxidant enzymes, in livers. The HFHCF-induced NASH increased intestinal permeability with abundant Facklamia and Aerococcus, an imbalanced gut environment that was significantly improved by the FMT, characterized with restoration of intestinal barrier function and an enrichment of Clostridium. Notably, the gut environment created by FMT was inferred to produce metabolites from the aromatic biogenic amine degradation pathway, specifically 4-hydroxyphenylacetic acid (4-HPA), which is known to ameliorate liver injury. We suggest that gut-derived molecules, related to hepatic improvement such as 4-HPA are the potential therapeutic agents for preventing and treating NASH.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad del Hígado Graso no Alcohólico
Aspecto:
Patient_preference
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Dig Liver Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2023
Tipo del documento:
Article
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS