Limosilactobacillus reuteri HM108 Alleviates Hyperuricemia in Honeybees through Degradation of Intestinal Purines.

Abstract Hyperuricemia is a prevalent metabolic disorder associated with gout and systemic inflammation, underscoring the urgent need for safe and effective therapeutic strategies. Probiotics derived from human milk have garnered considerable interest due to their safety profile and potential urate-lowering effects. This study evaluated the ameliorative effects of human milk-derived Limosilactobacillus reuteri HM108 on hemolymph uric acid (UA) levels and intestinal inflammation using a hyperuricemic honeybee model, and further explored the underlying mechanisms. Newly emerged worker bees were divided into three groups: control (CON), hyperuricemia model (HUA, fed a yeast RNA diet), and HM108 intervention (HUA diet + HM108). After 12 days, hemolymph UA levels and intestinal inflammatory gene expression were assessed. Multi-omics approaches including metabolomics, transcriptomics, and metagenomics were integrated to investigate the mechanisms. The results showed that the HUA group had a significant increase in hemolymph UA (+33.19%, P < 0.01) and pronounced upregulation of pro-inflammatory genes (Wnt-Rho1, PGRP-LC, Atg1, MAPK-phl, Toll). HM108 intervention restored UA to CON levels and reversed the expression of inflammatory genes. Metabolomics revealed significant enrichment of purine/pyrimidine metabolism pathways and UA precursors (e.g., guanine, hypoxanthine) in the HUA group, which were significantly suppressed by HM108. Metagenomics confirmed successful colonization of HM108, whose abundance was negatively correlated with UA levels, and revealed that HM108 alleviated HUA-induced gut microbiota dysbiosis. In conclusion, HM108 ameliorates hyperuricemia by degrading intestinal purines, reducing UA synthesis, attenuating inflammation, and modulating gut microbiota, demonstrating its potential as a functional food or therapeutic agent.