Frontiers in Immunology (Mar 2023)

Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization

  • Tianzhichao Hou,
  • Tianzhichao Hou,
  • Huajie Dai,
  • Huajie Dai,
  • Qi Wang,
  • Qi Wang,
  • Yanan Hou,
  • Yanan Hou,
  • Xiaoyun Zhang,
  • Xiaoyun Zhang,
  • Hong Lin,
  • Hong Lin,
  • Shuangyuan Wang,
  • Shuangyuan Wang,
  • Mian Li,
  • Mian Li,
  • Zhiyun Zhao,
  • Zhiyun Zhao,
  • Jieli Lu,
  • Jieli Lu,
  • Yu Xu,
  • Yu Xu,
  • Yuhong Chen,
  • Yuhong Chen,
  • Yanyun Gu,
  • Yanyun Gu,
  • Jie Zheng,
  • Jie Zheng,
  • Tiange Wang,
  • Tiange Wang,
  • Weiqing Wang,
  • Weiqing Wang,
  • Yufang Bi,
  • Yufang Bi,
  • Guang Ning,
  • Guang Ning,
  • Min Xu,
  • Min Xu

DOI
https://doi.org/10.3389/fimmu.2023.1148591
Journal volume & issue
Vol. 14

Abstract

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ObjectivesOur aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.MethodsWe extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.ResultsTwo taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.ConclusionsGut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.

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