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

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-pr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nan-Nan Li, Wei Li, Jun-Xia Feng, Bing Du, Rui Zhang, Shu-Heng Du, Shi-Yu Liu, Guan-Hua Xue, Chao Yan, Jing-Hua Cui, Han-Qing Zhao, Yan-Ling Feng, Lin Gan, Qun Zhang, Wei-Wei Zhang, Di Liu, Chen Chen, Jing Yuan
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	hialc kpn 2,3-butanediol fermentation pathway fld ethanol 2,3-butanediol Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/d277ad9fbdd547bb95351397b4c7bf9d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d277ad9fbdd547bb95351397b4c7bf9d
record_format	dspace
spelling	oai:doaj.org-article:d277ad9fbdd547bb95351397b4c7bf9d2021-11-26T11:19:48ZHigh alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo1949-09761949-098410.1080/19490976.2021.1979883https://doaj.org/article/d277ad9fbdd547bb95351397b4c7bf9d2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1979883https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984High 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.Nan-Nan LiWei LiJun-Xia FengBing DuRui ZhangShu-Heng DuShi-Yu LiuGuan-Hua XueChao YanJing-Hua CuiHan-Qing ZhaoYan-Ling FengLin GanQun ZhangWei-Wei ZhangDi LiuChen ChenJing YuanTaylor & Francis Grouparticlehialc kpn2,3-butanediol fermentation pathwayfldethanol2,3-butanediolDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hialc kpn 2,3-butanediol fermentation pathway fld ethanol 2,3-butanediol Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	hialc kpn 2,3-butanediol fermentation pathway fld ethanol 2,3-butanediol Diseases of the digestive system. Gastroenterology RC799-869 Nan-Nan Li Wei Li Jun-Xia Feng Bing Du Rui Zhang Shu-Heng Du Shi-Yu Liu Guan-Hua Xue Chao Yan Jing-Hua Cui Han-Qing Zhao Yan-Ling Feng Lin Gan Qun Zhang Wei-Wei Zhang Di Liu Chen Chen Jing Yuan High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
description	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.
format	article
author	Nan-Nan Li Wei Li Jun-Xia Feng Bing Du Rui Zhang Shu-Heng Du Shi-Yu Liu Guan-Hua Xue Chao Yan Jing-Hua Cui Han-Qing Zhao Yan-Ling Feng Lin Gan Qun Zhang Wei-Wei Zhang Di Liu Chen Chen Jing Yuan
author_facet	Nan-Nan Li Wei Li Jun-Xia Feng Bing Du Rui Zhang Shu-Heng Du Shi-Yu Liu Guan-Hua Xue Chao Yan Jing-Hua Cui Han-Qing Zhao Yan-Ling Feng Lin Gan Qun Zhang Wei-Wei Zhang Di Liu Chen Chen Jing Yuan
author_sort	Nan-Nan Li
title	High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
title_short	High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
title_full	High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
title_fullStr	High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
title_full_unstemmed	High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
title_sort	high alcohol-producing klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/d277ad9fbdd547bb95351397b4c7bf9d
work_keys_str_mv	AT nannanli highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT weili highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT junxiafeng highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT bingdu highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT ruizhang highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT shuhengdu highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT shiyuliu highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT guanhuaxue highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT chaoyan highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT jinghuacui highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT hanqingzhao highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT yanlingfeng highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT lingan highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT qunzhang highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT weiweizhang highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT diliu highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT chenchen highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo AT jingyuan highalcoholproducingklebsiellapneumoniaecausesfattyliverdiseasethrough23butanediolfermentationpathwayinvivo
_version_	1718409501075308544

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

Ejemplares similares