Lacticaseibacillus paracasei JS-3 Isolated from "Jiangshui" Ameliorates Hyperuricemia by Regulating Gut Microbiota and iTS Metabolism.

Abstract

Background: A diet high in purines can impair the function of the gut microbiota and disrupt purine metabolism, which is closely associated with the onset of hyperuricemia. Dietary regulation and intestinal health maintenance are key approaches for controlling uric acid (UA) levels. Investigating the impacts of fermented foods offers potential dietary interventions for managing hyperuricemia. Methods: In this study, we isolated a strain with potent UA-degrading capabilities from "Jiangshui", a fermented food product from Gansu, China. We performed strain identification and assessed its probiotic potential. Hyperuricemic quails, induced by a high-purine diet, were used to assess the UA degradation capability of strain JS-3 by measuring UA levels in serum and feces. Additionally, the UA degradation pathways were elucidated through analyses of the gut microbiome and fecal metabolomics. Results: JS-3, identified as Lacticaseibacillus paracasei, was capable of eliminating 16.11% of uric acid (UA) within 72 h, rapidly proliferating and producing acid within 12 h, and surviving in the gastrointestinal tract. Using hyperuricemic quail models, we assessed JS-3's UA degradation capacity. Two weeks after the administration of JS-3 (2 × 108 cfu/d per quail), serum uric acid (SUA) levels significantly decreased to normal levels, and renal damage in quails was markedly improved. Concurrently, feces from the JS-3 group demonstrated a significant degradation of UA, achieving up to 49% within 24 h. 16S rRNA sequencing revealed JS-3's role in gut microbiota restoration by augmenting the probiotic community (Bifidobacterium, Bacteroides unclassified_f-Lachnospiraceae, and norank_fynorank_o-Clostridia_UCG-014) and diminishing the pathogenic bacteria (Macrococus and Lactococcus). Corresponding with the rise in short-chain fatty acid (SCFA)-producing bacteria, JS-3 significantly increased SCFA levels (p < 0.05, 0.01). Additionally, JS-3 ameliorated metabolic disturbances in hyperuricemic quails, influencing 26 abnormal metabolites predominantly linked to purine, tryptophan, and bile acid metabolism, thereby enhancing UA degradation and renal protection. Conclusions: For the first time, we isolated and identified an active probiotic strain, JS-3, from the "Jiangshui" in Gansu, used for the treatment of hyperuricemia. It modulates host-microbiome interactions, impacts the metabolome, enhances intestinal UA degradation, reduces levels of SUA and fecal UA, alleviates renal damage, and effectively treats hyperuricemia without causing gastrointestinal damage. In summary, JS-3 can serve as a probiotic with potential therapeutic value for the treatment of hyperuricemia.