Page 70 - EJMO-9-2

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

subfamily G member 2 (ABCG2), play a substantial role ecosystem in managing HUA. Further research is essential
in the pathogenesis of HUA, with approximately 90% to fully understand the interplay between UA metabolism
of cases having a genetic component. Concurrently, and the gut microbiota and to explore potential therapeutic
1-6
environmental contributors, including dietary patterns, interventions targeting gut microbiota dysbiosis in the
lifestyle choices, age, and gender, significantly influence context of HUA and its associated disorders.
HUA development. Many studies have demonstrated
that diet and dietary components have profound effects 2. The mechanism of gut microbiota
on the composition of the gut microbiota and are among affecting purine metabolism
the most important contributors to alterations in bacterial The gut microbiota, a complex microbial community
flora. 7-9
colonizing the intestines, is crucial for regulating UA
The modern dietary trend toward increased metabolism. Dysregulation of the gut microbiota can
consumption of sugars, fats, and purine-rich foods can disrupt UA homeostasis, leading to HUA – a condition
perturb the gut microbiota composition, affecting nutrient characterized by elevated blood UA levels (Figure 1).
metabolism, immune regulation, and inflammatory The adult gut microbiota primarily comprises Firmicutes
responses, ultimately contributing to metabolic disorders, (approximately 64%) and Bacteroidetes (approximately
including HUA. The prevalence of HUA varies by region 28%), with a total abundance reaching around 10
14
and demographic, with higher rates in European and microorganisms. Bacteria within the gut microbiota have
American countries and geographic differences observed developed adaptive mechanisms for de novo biosynthesis
within Chinese populations. 10-12 and purine salvage, influencing UA metabolism. In
Mounting scientific evidence and clinical data addition, the gut microbiota can produce substrates that
underscore a close link between the onset and progression may enter the liver through the portal vein, leading to
of HUA and alterations in the intestinal microbiota’s the production of new purine amino acids and UA. 28-31
prevalence, distribution, and structural transformations. Metabolites (cysteine, glutamine, phenylalanine, etc.)
The gut microbiota is integral to regulating the host’s were significantly associated with UA change and incident
metabolic functions and immune system. Dysbiosis, HUA. Amino acid metabolism appears to play a critical
or disruption of the microbial equilibrium, can disturb role. Impairment of intestinal integrity and profound
multiple physiological metabolic pathways, including alterations in the profile of the solute carrier family resulted
the UA metabolic cascade. The enzyme xanthine oxidase in dysregulation of amino acid transportation. 32-35
(XO), a key player in UA biosynthesis, is expressed in Recent research suggests that the gut plays a pivotal
hepatocytes and exhibits peak expression in the duodenum role in the pathogenesis of HUA. Intestinal flora actively
and jejunum. In addition, certain gastrointestinal strains participates in purine metabolism and UA degradation. UA
of Escherichia coli can secrete xanthine dehydrogenase transporters located in intestinal epithelial cells facilitate
(XOD), contributing to purine catabolism. 13-23
the transport of UA from the bloodstream into the intestinal
The gastrointestinal tract plays a crucial role in lumen. Key transporters involved in this process include
maintaining UA homeostasis beyond the kidneys’ primary ABCG2 and SLC2A9. 36-39 Elevated UA levels can induce
role in urate excretion. Probiotics within the gut can inflammation through the toll-like receptors 4/NOD-like
degrade urate, and the consumption of Lactobacillus receptor protein 3 signaling pathway, adversely affecting
gasseri PA-3 has been associated with reduced serum UA intestinal epithelial cells. This inflammation leads to
(SUA) levels and stabilized gut microbiota by decreasing mitochondrial dysfunction and activation of the NF-κB
purine absorption. Disruption of the gut microbiota can signaling pathway, resulting in decreased expression of
affect the function of urate transporters on intestinal tight junction proteins and compromised integrity of the
epithelial cells, influencing UA transport and elimination. intestinal mucosal barrier. Consequently, the function of
Distinct differences in the abundance of intestinal flora
between healthy individuals and those with HUA have
been observed, with certain species such as Prevotella,
Akkermansia, and Barnesiella being linked to HUA. 24-27
HUA is a complex condition influenced by genetic and
environmental factors, with diet and lifestyle habits playing
significant roles. The balance between UA synthesis and
excretion pathways is influenced by the gut microbiota,
highlighting the importance of maintaining a healthy gut Figure 1. Structural formula of uric acid

Volume 9 Issue 2 (2025) 62 doi: 10.36922/ejmo.8579