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Fecal microbiota transplantation improves hepatic fibro-inflammation via regulating oxidative stress in experimental NASH

Authors
 Da Hyun Lee  ;  Jai J Jee  ;  Yu Seol Lee  ;  Da Ye Kim  ;  Ji Yun Bang  ;  Hye Won Lee  ;  Hong Koh  ;  Soo Han Bae 
Citation
 DIGESTIVE AND LIVER DISEASE, Vol.55(11) : 1521-1532, 2023-12 
Journal Title
DIGESTIVE AND LIVER DISEASE
ISSN
 1590-8658 
Issue Date
2023-12
MeSH
Animals ; Fecal Microbiota Transplantation ; Humans ; Inflammation / pathology ; Inflammation / therapy ; Mice ; Non-alcoholic Fatty Liver Disease* / therapy ; Oxidative Stress
Keywords
Fecal microbiota transplantation ; Gastrointestinal microbiome ; Gut microbiota metabolites ; Nonalcoholic steatohepatitis
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.
Files in This Item:
T202306157.pdf Download
DOI
10.1016/j.dld.2023.06.015
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Koh, Hong(고홍) ORCID logo https://orcid.org/0000-0002-3660-7483
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
Lee, Da Hyun(이다현) ORCID logo https://orcid.org/0000-0002-5412-6878
Lee, Hye Won(이혜원) ORCID logo https://orcid.org/0000-0002-3552-3560
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196738
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