Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia

Cell Host Microbe. 2024 Mar 13;32(3):366-381.e9. doi: 10.1016/j.chom.2024.02.001. Epub 2024 Feb 26.


Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.

Keywords: ABCG2; Alistipes indistinctus; gut microbiota; hippuric acid; hyperuricemia.

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Bacteroidetes*
  • Hippurates*
  • Humans
  • Hyperuricemia* / metabolism
  • Intestines
  • Uric Acid / metabolism


  • Uric Acid
  • hippuric acid
  • ATP-Binding Cassette Transporters
  • Hippurates

Supplementary concepts

  • Alistipes indistinctus