Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. / Wang, Xifan; Yang, Songtao; Li, Shenghui; Zhao, Liang; Hao, Yanling; Qin, Junjie; Zhang, Lian; Zhang, Chengying; Bian, Weijing; Zuo, L. I.; Gao, Xiu; Zhu, Baoli; Lei, Xingen; Gu, Zhenglong; Cui, Wei; Xu, Xiping; Li, Zhiming; Zhu, Benzhong; Li, Yuan; Chen, Shangwu; Guo, Huiyuan; Zhang, Hao; Sun, Jing; Zhang, Ming; Hui, Yan; Zhang, Xiaolin; Liu, Xiaoxue; Sun, Bowen; Wang, Longjiao; Qiu, Qinglu; Zhang, Yuchan; Li, Xingqi; Liu, Weiqian; Xue, Rui; Wu, Hong; Shao, Donghua; Li, Junling; Zhou, Yuanjie; Li, Shaochuan; Yang, Rentao; Pedersen, Oluf Borbye; Yu, Zhengquan; Ehrlich, Stanislav Dusko; Ren, Fazheng.
I: Gut, Bind 69, Nr. 12, 319766, 2020, s. 2131-2142.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
AU - Wang, Xifan
AU - Yang, Songtao
AU - Li, Shenghui
AU - Zhao, Liang
AU - Hao, Yanling
AU - Qin, Junjie
AU - Zhang, Lian
AU - Zhang, Chengying
AU - Bian, Weijing
AU - Zuo, L. I.
AU - Gao, Xiu
AU - Zhu, Baoli
AU - Lei, Xingen
AU - Gu, Zhenglong
AU - Cui, Wei
AU - Xu, Xiping
AU - Li, Zhiming
AU - Zhu, Benzhong
AU - Li, Yuan
AU - Chen, Shangwu
AU - Guo, Huiyuan
AU - Zhang, Hao
AU - Sun, Jing
AU - Zhang, Ming
AU - Hui, Yan
AU - Zhang, Xiaolin
AU - Liu, Xiaoxue
AU - Sun, Bowen
AU - Wang, Longjiao
AU - Qiu, Qinglu
AU - Zhang, Yuchan
AU - Li, Xingqi
AU - Liu, Weiqian
AU - Xue, Rui
AU - Wu, Hong
AU - Shao, Donghua
AU - Li, Junling
AU - Zhou, Yuanjie
AU - Li, Shaochuan
AU - Yang, Rentao
AU - Pedersen, Oluf Borbye
AU - Yu, Zhengquan
AU - Ehrlich, Stanislav Dusko
AU - Ren, Fazheng
PY - 2020
Y1 - 2020
N2 - Objective: Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD). Design: Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity. Results: A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-Treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats. Conclusion: Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients. Trial registration number: This study was registered at ClinicalTrials.gov (NCT03010696).
AB - Objective: Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD). Design: Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity. Results: A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-Treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats. Conclusion: Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients. Trial registration number: This study was registered at ClinicalTrials.gov (NCT03010696).
KW - bile acid
KW - enteric bacterial microflora
U2 - 10.1136/gutjnl-2019-319766
DO - 10.1136/gutjnl-2019-319766
M3 - Journal article
C2 - 32241904
AN - SCOPUS:85083286914
VL - 69
SP - 2131
EP - 2142
JO - Gut
JF - Gut
SN - 0017-5749
IS - 12
M1 - 319766
ER -
ID: 240149643