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High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
- Source :
- Gut Microbes, Vol 13, Iss 1 (2021)
- Publication Year :
- 2021
- Publisher :
- Taylor & Francis Group, 2021.
-
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.
- Subjects :
- Microbiology (medical)
Klebsiella pneumoniae
RC799-869
Gut flora
digestive system
Microbiology
fld
chemistry.chemical_compound
In vivo
2,3-Butanediol
medicine
2,3-butanediol fermentation pathway
Ethanol
biology
Catabolism
fungi
Fatty liver
Gastroenterology
2,3-butanediol
Diseases of the digestive system. Gastroenterology
biology.organism_classification
medicine.disease
hialc kpn
Infectious Diseases
chemistry
Fermentation
ethanol
Subjects
Details
- Language :
- English
- ISSN :
- 19490984 and 19490976
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Gut Microbes
- Accession number :
- edsair.doi.dedup.....b9c8e8bfa03943d4561bad6d24703ea8