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High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo.


ABSTRACT: High alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production in vivo remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) Kpn and constructed an adh (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc Kpn W14 strain (W14Δadh) using CRISPR-Cas9 system. Subsequently, we established the mouse model via gavage administration of HiAlc Kpn W14 and W14 Δadh strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc Kpn W14-fed mice, W14Δadh-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol via the 2,3-butanediol fermentation pathway in HiAlc Kpn, which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes in vivo.

SUBMITTER: Li NN 

PROVIDER: S-EPMC8510565 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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High alcohol-producing <i>Klebsiella pneumoniae</i> causes fatty liver disease through 2,3-butanediol fermentation pathway <i>in vivo</i>.

Li Nan-Nan NN   Li Wei W   Feng Jun-Xia JX   Zhang Wei-Wei WW   Zhang Rui R   Du Shu-Heng SH   Liu Shi-Yu SY   Xue Guan-Hua GH   Yan Chao C   Cui Jing-Hua JH   Zhao Han-Qing HQ   Feng Yan-Ling YL   Gan Lin L   Zhang Qun Q   Chen Chen C   Liu Di D   Yuan Jing J  

Gut microbes 20210101 1


High alcohol-producing <i>Klebsiella pneumoniae</i> (HiAlc <i>Kpn</i>) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production <i>in vivo</i> remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) <i>Kpn</i> and constructed an <i>adh</i> (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc <i>Kpn</i> W14 strain (W14<i>Δadh</i>) using CRISPR-Ca  ...[more]

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