Raw sequence reads of fecal metagenomics in HUA population
Hyperuricemia, characterized by an imbalance between uric acid (UA) generation and excretion, has become the second most common metabolic disease. In addition to gout, hyperuricemia has also been linked to the development of inflammatory arthritis, renal and cardiovascular diseases, posing a major threat to all societies. Despite a clear pharmacological mechanism for existing hypouricemic agents, severe side effects remain a major concern in their clinical implementation. Clearly, identifying safe and effective alternatives has the potential to significantly impact the quality of life for millions, and ameliorate the global burden of hyperuricemia and associated diseases.Recently, a growing body of evidence suggests that dysbiosis of gut microbiota plays an important role in the pathogenesis of hyperuricemia. Altered compositions of microbiota, characterized by a reduced abundance of genus Coprococcus, were found in subjects with hyperuricemia compared to those with normouricemia. Similarly, levels of some genera, such as Prevotella, Dehalobacterium, Ruminococcus, and Lactobacillus, were remarkably lower in rat model of hyperuricemia. Moreover, the phenotype of elevated UA was transmissible with fecal microbial transplantation from donors with hyperuricemia, whereas, supplementation of Bifidobacteria and Lactobacilli, two well-known probiotics, was effective to reduce UA in mice. However, murine models failed to fully replicate UA metabolism in humans, and the cross-sectional nature of existing human studies with several comorbidities but no biological validation precluded casual inference. Therefore, though emerging studies suggest that gut microbiota might be a novel therapeutic target for the management of hyperuricemia, specific species involved and their exact roles remain unclear.To address the questions above, an integrative analysis of metagenomics and metabolomics in medication-naive subjects with or without hyperuricemia was performed.