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Eurasian Journal of
Medicine and Oncology Gut microbiota and hyperuricemia: Mechanisms and therapeutic strategies

UA transporters in intestinal epithelial cells is impaired, of intestinal-derived LPS into the bloodstream may
leading to disorders in intestinal UA excretion. 40,41 increase the risk of gout in geese. 45-48
The gut microbiota also participates in the oxidative Further investigation is required to fully understand
metabolism of purine. Certain bacteria, such as E. coli and the complex interplay between the gut microbiota and UA
Proteus, can secrete XO, a key enzyme in purine oxidation. metabolism. However, emerging evidence suggests that the
Studies have demonstrated that gut microbiota is involved gut microbiota plays a significant role in the pathogenesis
in the catabolism of purine and UA through the secretion of HUA. This knowledge opens new avenues for the
of active enzymes. An imbalance in the gut microbiota development of targeted therapies for HUA, focusing on
can lead to an increase in the abundance of microbiota modulating the gut microbiota to restore UA homeostasis
associated with the XO gene, a decrease in the abundance and mitigate the associated health risks (Figure 2).
of microbiota associated with the allantoinase gene, and an
overall increase in intestinal UA levels. This imbalance is 3. Changes of gut microbiota in HUA
also closely associated with a decrease in short-chain fatty The intricate relationship between UA metabolism and gut
acids (SCFAs), which play a crucial role in maintaining gut microbiota involves a bidirectional interaction that can
health and regulating inflammation. 42-44 influence both the host’s gut environment and UA levels. Liu
Beyond direct involvement in purine metabolism, the et al. conducted a screening process within the repository
49
gut microbiota can also regulate systemic metabolism of human intestinal bacteria. By utilizing stable isotope
through purinergic receptors in the gut and the release tracing techniques, 46 species of UA-degrading bacteria
of extracellular adenosine triphosphate and nucleotide were identified, spanning four phyla: Actinobacteria,
metabolites. Firmicutes, Clostridia, and Proteobacteria.
Research has revealed a significant increase in serum Elevated UA can disrupt the gut microbiota, leading
lipopolysaccharide (LPS) levels in gouty geese that is to dysbiosis, while alterations in the microbiota can
attributed to intestinal dysbiosis, leading to increased further affect UA metabolism. This interaction impacts
intestinal barrier permeability. The enhanced translocation host health, as the gut microbiota plays a key role in UA

Figure 2. Schematic diagram of the metabolism of uric acid. Hyperuricemia is an imbalance in uric acid metabolism that includes increased uric acid
production through endogenous or exogenous purine metabolism and decreased renal and extrarenal excretion of uric acid, or both. Intestinal flora can
affect the metabolism of uric acid. The figure was created using Biorender.
Abbreviations: ABCG2: ATP-binding cassette, subfamily G, 2; AMP: Adenosine monophosphate; GLUT9: Glucose transporter 9; GMP: Guanine
monophosphate; IMP: Inosine monophosphate; OAT1: Organic anion transporter 1; OAT3: Organic anion transporter 3; PRPP: Phosphor-ribosyl-
pyrophosphate; UA: Uric acid; URAT1: Urate transporter 1.

Volume 9 Issue 2 (2025) 63 doi: 10.36922/ejmo.8579