Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
| Autor: | Xiu Gao, Junjie Qin, Junling Li, Longjiao Wang, Xiaolin Zhang, Rui Xue, Yuchan Zhang, Fazheng Ren, Xin Gen Lei, Yanling Hao, Yuanjie Zhou, Lian Zhang, Zhiming Li, Xiaoxue Liu, Shenghui Li, Xingqi Li, Liang Zhao, Yuan Li, Huiyuan Guo, Wei Cui, Jing Sun, Weiqian Liu, Yan Hui, Zhengquan Yu, Shangwu Chen, Zhenglong Gu, Weijing Bian, Benzhong Zhu, Li Zuo, DongHua Shao, Baoli Zhu, Shaochuan Li, Bowen Sun, Qinglu Qiu, Rentao Yang, Xifan Wang, Hao Zhang, Stanislav Dusko Ehrlich, Songtao Yang, Xiping Xu, Hong Wu, Ming Zhang, Chengying Zhang, Oluf Pedersen |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine 030232 urology & nephrology Gut flora urologic and male genital diseases medicine.disease_cause law.invention Bile Acids and Salts Feces Mice 03 medical and health sciences Probiotic 0302 clinical medicine law Renal fibrosis Metabolome Animals Humans bile acid Medicine Gut Microbiota Toxins Biological Uremia Gastroenterology & Hepatology biology business.industry Gastroenterology 1103 Clinical Sciences biology.organism_classification medicine.disease Gastrointestinal Microbiome Rats enteric bacterial microflora Bifidobacterium animalis Disease Models Animal Oxidative Stress 030104 developmental biology Case-Control Studies Immunology Kidney Failure Chronic 1114 Paediatrics and Reproductive Medicine Female Fusobacterium nucleatum business Oxidative stress Kidney disease |
| Zdroj: | Wang, X, Yang, S, Li, S, Zhao, L, Hao, Y, Qin, J, Zhang, L, Zhang, C, Bian, W, Zuo, L I, Gao, X, Zhu, B, Lei, X, Gu, Z, Cui, W, Xu, X, Li, Z, Zhu, B, Li, Y, Chen, S, Guo, H, Zhang, H, Sun, J, Zhang, M, Hui, Y, Zhang, X, Liu, X, Sun, B, Wang, L, Qiu, Q, Zhang, Y, Li, X, Liu, W, Xue, R, Wu, H, Shao, D, Li, J, Zhou, Y, Li, S, Yang, R, Pedersen, O B, Yu, Z, Ehrlich, S D & Ren, F 2020, ' Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents ', Gut, vol. 69, no. 12, 319766, pp. 2131-2142 . https://doi.org/10.1136/gutjnl-2019-319766 Gut |
| ISSN: | 1468-3288 0017-5749 |
| Popis: | ObjectivePatients 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).DesignCharacterisation 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.ResultsA 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.ConclusionAberrant 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 numberThis study was registered at ClinicalTrials.gov (NCT03010696). |
| Databáze: | OpenAIRE |
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