RT Journal Article
SR Electronic
T1 Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 2131
OP 2142
DO 10.1136/gutjnl-2019-319766
VO 69
IS 12
A1 Xifan Wang
A1 Songtao Yang
A1 Shenghui Li
A1 Liang Zhao
A1 Yanling Hao
A1 Junjie Qin
A1 Lian Zhang
A1 Chengying Zhang
A1 Weijing Bian
A1 Li Zuo
A1 Xiu Gao
A1 Baoli Zhu
A1 Xin Gen Lei
A1 Zhenglong Gu
A1 Wei Cui
A1 Xiping Xu
A1 Zhiming Li
A1 Benzhong Zhu
A1 Yuan Li
A1 Shangwu Chen
A1 Huiyuan Guo
A1 Hao Zhang
A1 Jing Sun
A1 Ming Zhang
A1 Yan Hui
A1 Xiaolin Zhang
A1 Xiaoxue Liu
A1 Bowen Sun
A1 Longjiao Wang
A1 Qinglu Qiu
A1 Yuchan Zhang
A1 Xingqi Li
A1 Weiqian Liu
A1 Rui Xue
A1 Hong Wu
A1 DongHua Shao
A1 Junling Li
A1 Yuanjie Zhou
A1 Shaochuan Li
A1 Rentao Yang
A1 Oluf Borbye Pedersen
A1 Zhengquan Yu
A1 Stanislav Dusko Ehrlich
A1 Fazheng Ren
YR 2020
UL http://gut.bmj.com/content/69/12/2131.abstract
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).