Background/Objectives: Hyperuricemia (HUA) is the second most common metabolic disease in China (24.5% in males, 3.6% in females), which can induce multiple complications such as gout and diabetes. Existing urate-lowering drugs have significant hepatorenal toxicity, necessitating safe lifestyle interventions. Electrolyzed alkaline water (EAW) as daily drinking water has shown preliminary effectiveness, but it lacks randomized controlled evidence and mechanistic studies at the microbiome–metabolome interface. Methods: We conducted a 12-week randomized controlled trial in 40 adults aged 18–65 years with elevated serum uric acid (SUA). Participants consumed either 1.5 L/day of EAW (pH 8.5–9.5) or purified water (pH 7.0). Clinical indicators, quality of life (SF-36), gut microbiota, and gut metabolomics were comprehensively assessed to evaluate intervention efficacy and explore potential mechanisms. Results: After 12 weeks, the EAW group exhibited a larger reduction in serum uric acid than the control group, along with improvements in selected physical health-related quality-of-life measures. Modest differences in gut microbial composition were observed between groups. Metabolomic analyses identified group-level differences in metabolites enriched in pathways related to purine metabolism and other urate-associated metabolic processes. Conclusions: This pilot randomized controlled trial suggests that consumption of EAW is associated with a modest reduction in serum uric acid. Exploratory multi-omics analyses indicate concurrent changes in gut microbiota and metabolic profiles. These findings support further investigation of electrolyzed alkaline water as a potential adjunctive, non-pharmacological option for hyperuricemia in larger and longer-term studies. Ethics: This trial was registered with the Chinese Clinical Trial Registry under the identifier ChiCTR2500100190. Ethical approval for the present study was granted by the Nankai University Institutional Review Board (NKUIRB2025001, 23 January 2025).

Phage-derived endolysins are considered promising antibacterial agents for controlling bacterial pathogens. However, their activity against Gram-negative bacteria is usually limited by the outer membrane barrier. Salmonella enterica is a leading foodborne pathogen and an important target for endolysin-based control strategies. In this study, we identified and characterized LysSPYS2, an endolysin encoded by Salmonella phage SPYS_2. Recombinant LysSPYS2 was expressed in Escherichia coli Rosetta(DE3) and purified for activity assays. The optical density at 600 nm (OD₆₀₀)-based turbidity-reduction activity, temperature and pH dependence under the tested conditions, and lytic spectrum of LysSPYS2 were determined using permeabilized bacterial suspensions. LysSPYS2 showed concentration-dependent turbidity reduction against Salmonella enterica serovar Typhimurium ATCC 14028, with the highest observed activity at 42 °C and pH 7. LysSPYS2 also showed lytic activity against several Gram-negative bacteria, with stronger activity against Salmonella strains. In intact-cell broth assays, LysSPYS2 alone showed limited growth suppression, whereas its growth-suppressive effect was enhanced when combined with polymyxin B or magnolol. These results suggest that LysSPYS2 may be further evaluated as a component of combination-based Salmonella control strategies.