Abstract

Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn-induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn-induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn-caused NAFLD.

Previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Here, the authors show the effectiveness of phage in mice with HiAlc Kpn-induced NAFLD indicating phage therapy targeting gut microbiota may be an alternative to antibiotics, with potential efficacy and safety.

Details

Title
Bacteriophage targeting microbiota alleviates non-alcoholic fatty liver disease induced by high alcohol-producing Klebsiella pneumoniae
Author
Gan, Lin 1 ; Feng, Yanling 1 ; Du, Bing 1 ; Fu, Hanyu 1 ; Tian, Ziyan 1 ; Xue, Guanhua 1 ; Yan, Chao 1 ; Cui, Xiaohu 1 ; Zhang, Rui 1 ; Cui, Jinghua 1 ; zhao, Hanqing 1 ; Feng, Junxia 1 ; Xu, Ziying 1 ; Fan, Zheng 1 ; Fu, Tongtong 1 ; Du, Shuheng 1 ; Liu, Shiyu 1 ; Zhang, Qun 1 ; Yu, Zihui 1 ; Sun, Ying 2 ; Yuan, Jing 1   VIAFID ORCID Logo 

 Capital Institute of Pediatrics, Department of Bacteriology, Beijing, China (GRID:grid.418633.b) (ISNI:0000 0004 1771 7032) 
 Capital Medical University, Department of Immunology, School of Basic Medical Sciences, Beijing, China (GRID:grid.24696.3f) (ISNI:0000 0004 0369 153X) 
Pages
3215
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2822005241
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.