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@article{Wang:2020:10.1136/gutjnl-2019-319766,
author = {Wang, X and Yang, S and Li, S and Zhao, L and Hao, Y and Qin, J and Zhang, L and Zhang, C and Bian, W and Zuo, L and Gao, X and Zhu, B and Lei, XG and Gu, Z and Cui, W and Xu, X and Li, Z and Zhu, B and Li, Y and Chen, S and Guo, H and Zhang, H and Sun, J and Zhang, M and Hui, Y and Zhang, X and Liu, X and Sun, B and Wang, L and Qiu, Q and Zhang, Y and Li, X and Liu, W and Xue, R and Wu, H and Shao, D and Li, J and Zhou, Y and Li, S and Yang, R and Pedersen, OB and Yu, Z and Ehrlich, SD and Ren, F},
doi = {10.1136/gutjnl-2019-319766},
journal = {Gut},
pages = {2131--2142},
title = {Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents},
url = {http://dx.doi.org/10.1136/gutjnl-2019-319766},
volume = {69},
year = {2020}
}

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TY  - JOUR
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).
AU  - Wang,X
AU  - Yang,S
AU  - Li,S
AU  - Zhao,L
AU  - Hao,Y
AU  - Qin,J
AU  - Zhang,L
AU  - Zhang,C
AU  - Bian,W
AU  - Zuo,L
AU  - Gao,X
AU  - Zhu,B
AU  - Lei,XG
AU  - Gu,Z
AU  - Cui,W
AU  - Xu,X
AU  - Li,Z
AU  - Zhu,B
AU  - Li,Y
AU  - Chen,S
AU  - Guo,H
AU  - Zhang,H
AU  - Sun,J
AU  - Zhang,M
AU  - Hui,Y
AU  - Zhang,X
AU  - Liu,X
AU  - Sun,B
AU  - Wang,L
AU  - Qiu,Q
AU  - Zhang,Y
AU  - Li,X
AU  - Liu,W
AU  - Xue,R
AU  - Wu,H
AU  - Shao,D
AU  - Li,J
AU  - Zhou,Y
AU  - Li,S
AU  - Yang,R
AU  - Pedersen,OB
AU  - Yu,Z
AU  - Ehrlich,SD
AU  - Ren,F
DO  - 10.1136/gutjnl-2019-319766
EP  - 2142
PY  - 2020///
SN  - 0017-5749
SP  - 2131
TI  - Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
T2  - Gut
UR  - http://dx.doi.org/10.1136/gutjnl-2019-319766
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32241904
UR  - http://hdl.handle.net/10044/1/78920
VL  - 69
ER  -

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