Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice
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 o...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.05349-22 |
| _version_ | 1797393586714574848 |
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| author | Ye Rin Park Hae Lee Lee Ji Ye Hyun Jieun Choi Ji Hyun Moon Byung Yong Kim Seung-Jo Yang Je Hee Lee Byoung Kook Kim Tae-Sik Park Ki Tae Suk Do Yup Lee |
| author_facet | Ye Rin Park Hae Lee Lee Ji Ye Hyun Jieun Choi Ji Hyun Moon Byung Yong Kim Seung-Jo Yang Je Hee Lee Byoung Kook Kim Tae-Sik Park Ki Tae Suk Do Yup Lee |
| author_sort | Ye Rin Park |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-03-09T00:06:00Z |
| format | Article |
| id | doaj.art-35983cb0982b4b63bd69d2060d060949 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:00Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-35983cb0982b4b63bd69d2060d0609492023-12-12T13:17:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.05349-22Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male miceYe Rin Park0Hae Lee Lee1Ji Ye Hyun2Jieun Choi3Ji Hyun Moon4Byung Yong Kim5Seung-Jo Yang6Je Hee Lee7Byoung Kook Kim8Tae-Sik Park9Ki Tae Suk10Do Yup Lee11Department of Agricultural Biotechnology, Seoul National University , Seoul, South KoreaDepartment of Agricultural Biotechnology, Seoul National University , Seoul, South KoreaInstitute for Liver and Digestive Diseases, Hallym University , Chuncheon, South KoreaDepartment of Agricultural Biotechnology, Seoul National University , Seoul, South KoreaDepartment of Agricultural Biotechnology, Seoul National University , Seoul, South KoreaR&D Center, Chong Kun Dang Healthcare , Seoul, South KoreaR&D Discovery Center, CJ Bioscience, Inc , Seoul, South KoreaR&D Discovery Center, CJ Bioscience, Inc , Seoul, South KoreaChong Kun Dang Bio Research Institute , Gyeonggi-do, South KoreaDepartment of Life Science, Gachon University , Sungnam, South KoreaInstitute for Liver and Digestive Diseases, Hallym University , Chuncheon, South KoreaDepartment of Agricultural Biotechnology, Seoul National University , Seoul, South KoreaABSTRACT 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).https://journals.asm.org/doi/10.1128/spectrum.05349-22liver cirrhosisBacteroidesmultiomicsgut-liver axismetabolomicsmicrobiome |
| spellingShingle | Ye Rin Park Hae Lee Lee Ji Ye Hyun Jieun Choi Ji Hyun Moon Byung Yong Kim Seung-Jo Yang Je Hee Lee Byoung Kook Kim Tae-Sik Park Ki Tae Suk Do Yup Lee Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice Microbiology Spectrum liver cirrhosis Bacteroides multiomics gut-liver axis metabolomics microbiome |
| title | Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice |
| title_full | Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice |
| title_fullStr | Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice |
| title_full_unstemmed | Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice |
| title_short | Systemic multiomics evaluation of the therapeutic effect of Bacteroides species on liver cirrhosis in male mice |
| title_sort | systemic multiomics evaluation of the therapeutic effect of bacteroides species on liver cirrhosis in male mice |
| topic | liver cirrhosis Bacteroides multiomics gut-liver axis metabolomics microbiome |
| url | https://journals.asm.org/doi/10.1128/spectrum.05349-22 |
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