Metagenomic analysis revealed the potential role of gut microbiome in gout

Abstract Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout pat...

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Autores principales: Yongliang Chu, Silong Sun, Yufen Huang, Qiang Gao, Xuefeng Xie, Peng Wang, Junxia Li, Lifeng Liang, Xiaohong He, Yiqi Jiang, Maojie Wang, Jianhua Yang, Xiumin Chen, Chu Zhou, Yue Zhao, Fen Ding, Yi Zhang, Xiaodong Wu, Xueyuan Bai, Jiaqi Wu, Xia Wei, Xianghong Chen, Zhen Yue, Xiaodong Fang, Qingchun Huang, Zhang Wang, Runyue Huang
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:84953369806a4b848260c00d038c60722021-12-02T16:27:55ZMetagenomic analysis revealed the potential role of gut microbiome in gout10.1038/s41522-021-00235-22055-5008https://doaj.org/article/84953369806a4b848260c00d038c60722021-08-01T00:00:00Zhttps://doi.org/10.1038/s41522-021-00235-2https://doaj.org/toc/2055-5008Abstract Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout patients and 86 healthy controls. Gout metagenomes significantly differed from those of healthy controls. The relative abundances of Prevotella, Fusobacterium, and Bacteroides were increased in gout, whereas those of Enterobacteriaceae and butyrate-producing species were decreased. Functionally, gout patients had greater abundances for genes in fructose, mannose metabolism and lipid A biosynthesis, and lower for genes in urate degradation and short chain fatty acid production. A three-pronged association between metagenomic species, functions and clinical parameters revealed that decreased abundances of species in Enterobacteriaceae were associated with reduced amino acid metabolism and environmental sensing, which together contribute to increased serum uric acid and C-reactive protein levels in gout. A random forest classifier based on three gut microbial genes showed high predictivity for gout in both discovery and validation cohorts (0.91 and 0.80 accuracy), with high specificity in the context of other chronic disorders. Longitudinal analysis showed that uric-acid-lowering and anti-inflammatory drugs partially restored gut microbiota after 24-week treatment. Comparative analysis with obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis indicated that gout metagenomes were more similar to those of autoimmune than metabolic diseases. Our results suggest that gut dysbiosis was associated with dysregulated host urate degradation and systemic inflammation and may be used as non-invasive diagnostic markers for gout.Yongliang ChuSilong SunYufen HuangQiang GaoXuefeng XiePeng WangJunxia LiLifeng LiangXiaohong HeYiqi JiangMaojie WangJianhua YangXiumin ChenChu ZhouYue ZhaoFen DingYi ZhangXiaodong WuXueyuan BaiJiaqi WuXia WeiXianghong ChenZhen YueXiaodong FangQingchun HuangZhang WangRunyue HuangNature PortfolioarticleMicrobial ecologyQR100-130ENnpj Biofilms and Microbiomes, Vol 7, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Microbial ecology
QR100-130
spellingShingle Microbial ecology
QR100-130
Yongliang Chu
Silong Sun
Yufen Huang
Qiang Gao
Xuefeng Xie
Peng Wang
Junxia Li
Lifeng Liang
Xiaohong He
Yiqi Jiang
Maojie Wang
Jianhua Yang
Xiumin Chen
Chu Zhou
Yue Zhao
Fen Ding
Yi Zhang
Xiaodong Wu
Xueyuan Bai
Jiaqi Wu
Xia Wei
Xianghong Chen
Zhen Yue
Xiaodong Fang
Qingchun Huang
Zhang Wang
Runyue Huang
Metagenomic analysis revealed the potential role of gut microbiome in gout
description Abstract Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout patients and 86 healthy controls. Gout metagenomes significantly differed from those of healthy controls. The relative abundances of Prevotella, Fusobacterium, and Bacteroides were increased in gout, whereas those of Enterobacteriaceae and butyrate-producing species were decreased. Functionally, gout patients had greater abundances for genes in fructose, mannose metabolism and lipid A biosynthesis, and lower for genes in urate degradation and short chain fatty acid production. A three-pronged association between metagenomic species, functions and clinical parameters revealed that decreased abundances of species in Enterobacteriaceae were associated with reduced amino acid metabolism and environmental sensing, which together contribute to increased serum uric acid and C-reactive protein levels in gout. A random forest classifier based on three gut microbial genes showed high predictivity for gout in both discovery and validation cohorts (0.91 and 0.80 accuracy), with high specificity in the context of other chronic disorders. Longitudinal analysis showed that uric-acid-lowering and anti-inflammatory drugs partially restored gut microbiota after 24-week treatment. Comparative analysis with obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis indicated that gout metagenomes were more similar to those of autoimmune than metabolic diseases. Our results suggest that gut dysbiosis was associated with dysregulated host urate degradation and systemic inflammation and may be used as non-invasive diagnostic markers for gout.
format article
author Yongliang Chu
Silong Sun
Yufen Huang
Qiang Gao
Xuefeng Xie
Peng Wang
Junxia Li
Lifeng Liang
Xiaohong He
Yiqi Jiang
Maojie Wang
Jianhua Yang
Xiumin Chen
Chu Zhou
Yue Zhao
Fen Ding
Yi Zhang
Xiaodong Wu
Xueyuan Bai
Jiaqi Wu
Xia Wei
Xianghong Chen
Zhen Yue
Xiaodong Fang
Qingchun Huang
Zhang Wang
Runyue Huang
author_facet Yongliang Chu
Silong Sun
Yufen Huang
Qiang Gao
Xuefeng Xie
Peng Wang
Junxia Li
Lifeng Liang
Xiaohong He
Yiqi Jiang
Maojie Wang
Jianhua Yang
Xiumin Chen
Chu Zhou
Yue Zhao
Fen Ding
Yi Zhang
Xiaodong Wu
Xueyuan Bai
Jiaqi Wu
Xia Wei
Xianghong Chen
Zhen Yue
Xiaodong Fang
Qingchun Huang
Zhang Wang
Runyue Huang
author_sort Yongliang Chu
title Metagenomic analysis revealed the potential role of gut microbiome in gout
title_short Metagenomic analysis revealed the potential role of gut microbiome in gout
title_full Metagenomic analysis revealed the potential role of gut microbiome in gout
title_fullStr Metagenomic analysis revealed the potential role of gut microbiome in gout
title_full_unstemmed Metagenomic analysis revealed the potential role of gut microbiome in gout
title_sort metagenomic analysis revealed the potential role of gut microbiome in gout
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/84953369806a4b848260c00d038c6072
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