Bacteriophage targeting microbiota alleviates non-alcoholic fatty liver disease induced by high alcohol-producing Klebsiella pneumoniae

Lin Gan, Yanling Feng, Bing Du, Hanyu Fu, Ziyan Tian, Guanhua Xue, Chao Yan, Xiaohu Cui, Rui Zhang, Jinghua Cui, Hanqing Zhao, Junxia Feng, Ziying Xu, Zheng Fan, Tongtong Fu, Shuheng Du, Shiyu Liu, Qun Zhang, Zihui Yu, Ying Sun () and Jing Yuan ()
Additional contact information
Lin Gan: Capital Institute of Pediatrics
Yanling Feng: Capital Institute of Pediatrics
Bing Du: Capital Institute of Pediatrics
Hanyu Fu: Capital Institute of Pediatrics
Ziyan Tian: Capital Institute of Pediatrics
Guanhua Xue: Capital Institute of Pediatrics
Chao Yan: Capital Institute of Pediatrics
Xiaohu Cui: Capital Institute of Pediatrics
Rui Zhang: Capital Institute of Pediatrics
Jinghua Cui: Capital Institute of Pediatrics
Hanqing Zhao: Capital Institute of Pediatrics
Junxia Feng: Capital Institute of Pediatrics
Ziying Xu: Capital Institute of Pediatrics
Zheng Fan: Capital Institute of Pediatrics
Tongtong Fu: Capital Institute of Pediatrics
Shuheng Du: Capital Institute of Pediatrics
Shiyu Liu: Capital Institute of Pediatrics
Qun Zhang: Capital Institute of Pediatrics
Zihui Yu: Capital Institute of Pediatrics
Ying Sun: Capital Medical University
Jing Yuan: Capital Institute of Pediatrics

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39028-w

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