Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury

Chun-Ju Yang; Hao-Chun Chang; Pin-Cheng Sung; Mao-Cheng Ge; Hsiang-Yu Tang; Mei-Ling Cheng; Hao-Tsai Cheng; Hong-Hsue Chou; Cheng-Yu Lin; Wey-Ran Lin; Yun-Shien Lee; Sen-Yung Hsieh

doi:10.1016/j.celrep.2023.113591

Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury

Cell Rep. 2024 Jan 23;43(1):113591. doi: 10.1016/j.celrep.2023.113591. Epub 2023 Dec 27.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou 333, Taiwan.
² Department of Biomedical Sciences, Chang Gung University, Taoyuan 333, Taiwan.
³ Department of Laboratory Medicine, Chang Gung University, Taoyuan 333, Taiwan; Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁴ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou 333, Taiwan; Devision of Gastroenterology and Hepatology, New Taipei Municipal TuCheng Hospital, New Taipei City 236, Taiwan; Grandulate Institute of Clinical Medicine, College of Medicine, Chang Gung University 333, Taoyuan, Taiwan.
⁵ Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁶ Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; Department of Biotechnology, Ming Chuan University, Taoyuan 333, Taiwan.
⁷ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou 333, Taiwan; Grandulate Institute of Clinical Medicine, College of Medicine, Chang Gung University 333, Taoyuan, Taiwan. Electronic address: siming@cgmh.org.tw.

PMID: 38153838
DOI: 10.1016/j.celrep.2023.113591

Abstract

While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury.

Keywords: CP: Cell biology; CP: Microbiology; DILI; FMT; Nrf2; acetaminophen; acute liver failure; drug-induced liver injury; fecal microbiota transplantation; ferroptosis; gut-liver axis; short-chain fatty acids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Butyrates*
Fecal Microbiota Transplantation*
Feces
Humans
Liver
Mice

Substances

Butyrates