Systemic multiomics evaluation of the therapeutic effect of
Bacteroides
species on liver cirrhosis in male mice
Authors: Park Ye Rin , Lee Hae Lee , Hyun Ji Ye , Choi Jieun , Moon Ji Hyun , Kim Byung Yong , Yang Seung-Jo , Lee Je Hee , Kim Byoung Kook , Park Tae-Sik , Suk Ki Tae , Lee Do Yup 
Published: October 2023

ABSTRACT

The human gut microbiome is engaged in biological homeostasis in the gut-liver axis and across multi-organs. The aim of this study is to investigate the therapeutic effects of human gut-derived microbes,
Bacteroides
species on liver cirrhosis in a mouse model. The experiment was performed on male mice, which were divided into five groups: normal control (NC), disease control,
Bacteroides dorei-
,
Bacteroides cellulosilyticus-
, and ursodeoxycholic acid-supplemented groups after 3,5-diethoxycarbonyl-1,4-dihydrocollidine treatment. The therapeutic effect was evaluated based on liver physiology and the expression level of hepatic fibrosis. Untargeted and targeted metabolic profiling was conducted on cecal, fecal, liver, and serum samples using ultra-performance liquid-chromatography coupled with high-resolution mass-spectrometry. The gut microbial taxonomic composition was analyzed by 16S rRNA gene amplicon sequencing from the stool of each mice group. The
Bacteroides
treatment improved the liver/body weight ratio and normalized hepatic fibrosis biomarkers, including COL1A1. The fecal metabolome showed the most distinctive and characteristic profiles according to different treatments, compared to other sample matrices (cecum, liver, and blood). Key metabolites were identified, which indicated the potential therapeutic effect of the
B. dorei
treatment. Among them, a short-chain fatty acid, propionic acid, showed consistent upregulation in the cecum and liver after the
B. dorei
treatment. Microbiome analysis showed that
Akkermansia muciniphila
was retained in the group treated with
B. dorei
at a similar level as in the NC group. Our current multiomics study of systemic dynamics demonstrated that
Bacteroides
species, particularly
B. dorei
, ameliorated liver cirrhosis by modulating the metabolic and microbial environment to the normal state within the gut-liver axis.

IMPORTANCE

The human gut microbiome mediates bidirectional interaction within the gut-liver axis, while liver diseases, including liver cirrhosis, are very closely related to the state of the gut environment. Thus, improving the health of the gut-liver axis by targeting the intestinal microbiota is a potential therapeutic approach in hepatic diseases. This study examines changes in metabolomics and microbiome composition by treating bacteria derived from the human gut in mice with liver cirrhosis. Interorgan-based multiomics profiling coupled with functional examination demonstrated that the treatment of
Bacteroides dorei
pertained to protective effects on liver cirrhosis by normalizing the functional, metabolic, and metagenomic environment through the gut-liver axis. The study provides the potential value of a multiomics-based and interorgan-targeted evaluation platform for the comprehensive examination and mechanistic understanding of a wide range of biologics, including gut microbes. Furthermore, the current finding also suggests in-depth future research focusing on the discovery and validation of next-generation probiotics and products (postbiotics).