POS0090 DYSBIOSIS OF GUT MICROBIOME, BILE ACID COMPOSITIONS, AND PREVALENCE OF HYPERURICEMIA: DATA FROM THE XIANGYA HYPERURICEMIA STUDY

Background

Hyperuricemia is a pre-requisite for gout, and often co-occurs with other metabolic diseases^[1]. Emerging evidence suggests that gut microbiota is an important factor in the development of metabolic diseases^[2]. Moreover, altered gut microbiota, ascertained using 16S rRNA-based sequencing method, has been linked to hyperuricemia^[3]. However, the 16S rRNA technique has limited resolution to differentiate closely related species. Therefore, the hyperuricemia associated specific species and underlying mechanism remain unclear. Additionally, cross-talk between bile acid metabolites and the gut microbiome has been implicated in metabolic diseases, implying potential effect of bile acid metabolism in the pathogenesis of hyperuricemia.

Objectives

The aim of this study was to examine the relation of gut microbiome based on shotgun metagenomic sequencing to prevalent hyperuricemia and potential mediators of bile acids.

Methods

Participants were derived from a community-based observational study, the Xiangya Hyperuricemia Study. Hyperuricemia was defined as serum urate level > 404 μmol/L. Gut microbial composition was determined using shotgun metagenomic sequencing and plasma bile acids were measured by high-performance liquid chromatography mass spectrometry. The Chao1 index (i.e., richness) and Shannon index (i.e., diversity) of microbial genes and taxa and the difference of microbial composition, indicated by Bray-Curtis distance between participants with and without hyperuricemia were assessed. The association between gut microbiome and prevalence of hyperuricemia and the extent to which the association was mediated by plasma bile acids were also evaluated.

Results

Among 1,379 participants, the prevalence of hyperuricemia was 13.4% (n = 185) (Figure 1 A). Decreased microbial richness and diversity, altered composition of gut microbiome and lower relative abundance of seventeen key species Coprococcus comes, Dorea longicatena, Desulfovibrio piger, Ruminococcus sp003526955, Holdemanella sp002299315, Ruminococcus sp000437175, Ruminococcus sp000437095, Coprococcus eutactus, Blautia sp900066335, Blautia sp900066205, Blautia sp900066505, Ruminococcus sp003011855, Blautia sp900120195, Blautia sp000285855, Dorea formicigenerans, Acetatifactor sp900066365 and Blautia wexlerae were significantly associated with prevalent hyperuricemia (Figure 1 B and C). High levels of taurochenodeoxycholic acid (TCDCA) and low levels of deoxycholic acid (DCA) were associated with high prevalence of hyperuricemia (Figure 1 D and E). Inversely associations between these key species and hyperuricemia were partially mediated through their effect on the levels of TCDCA and DCA. For instance, the indirect effects (OR) of relative abundance of Coprococcus comes on hyperuricemia through DCA and TCDCA were 0.97 (95% CI: 0.94 to 1.00) and 0.98 (95% CI: 0.97 to 1.00), respectively, and the corresponding percentage of mediation were 12.0% and 7.4% respectively. The indirect effects of Dorea longicatena on hyperuricemia via DCA and TCDCA were 0.97 (95% CI: 0.95 to 1.00) and 0.98 (95% CI: 0.97, 1.00), and the percentage of their mediation effect were 10.1% and 6.0%, respectively (Figure 1 F).

Conclusion

We identified several key species of gut microbiome for hyperuricemia and demonstrated that the association between gut microbiome dysbiosis and prevalent hyperuricemia is partially mediated via bile acids. These findings provide new sights into the role of microbiome and bile acids in the development of hyperuricemia and may contribute to translational opportunities.

References

[1]Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med 2012;125(7):679–87. [2]Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 2021;19(1):55–71. [3]Wei J, Zhang Y, Dalbeth N, et al. Association Between Gut Microbiota and Elevated Serum Urate in Two Independent Cohorts. Arthritis Rheumatol 2022;74(4):682–91.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (GL: 81930071, GL: U21A20352, CZ: 82072502), and the Project Program of National Clinical Research Center for Geriatric Disorders (CZ: 2022LNJJ07, JW: 2021LNJJ05).

Disclosure of Interests

Jie Wei: None declared, Yang Cui: None declared, Jing Wu: None declared, Ziying Wu: None declared, Yuqing Zhang: None declared, Nicola Dalbeth Grant/research support from: AstraZeneca, Dyve Biosciences, Horizon, Amgen, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, PTC Therapeutics, and Protalix, Robert Terkeltaub: None declared, Tuo Yang: None declared, Jiatian Li: None declared, Yuanheng Yang: None declared, Changjun Li: None declared, Chao Zeng: None declared, Guanghua Lei: None declared.