In Vitro and In Vivo Evaluation of Pediococcus acidilactici Pedio6-1 for Purine Metabolism Modulation in Diet-Induced Obese Mice

Gut lactic acid bacteria are emerging as potential targets for modulating host purine metabolism and alleviating hyperuricemia-related disorders. This study aimed to isolate purine-degrading lactic acid bacterial strains from porcine intestine and systematically evaluate their probiotic potential through both in vitro and in vivo approaches. A strain designated Pedio6-1 was isolated and identified as Pediococcus acidilactici based on 16S rRNA sequencing. In vitro assays demonstrated that P. acidilactici Pedio6-1 exhibited nearly complete adenine clearance (approaching 100%) and a total purine clearance rate of 30.73%, along with strong tolerance to acidic conditions, bile salts, and gastrointestinal enzymes. To further assess its in vivo efficacy, a high-fat diet-induced obese mouse model was employed. After 8 weeks of intervention, Pedio6-1 supplementation significantly reduced the final body weight and liver index, and markedly decreased hepatic guanine levels (p < 0.05), with a trend toward lower total purine content compared to the obese control group. Mechanistically, Pedio6-1 treatment significantly downregulated the hepatic mRNA expression of pro-inflammatory cytokines IL-1β and TLR4 (p < 0.05). Serum untargeted metabolomics revealed that Pedio6-1 treatment shifted the metabolic profile toward that of normal diet-fed mice, with differential pathways predominantly enriched in porphyrin metabolism and amino acid biosynthesis and metabolism. Notably, key metabolites with antioxidant and metabolic regulatory functions, including bilirubin, biliverdin, glutathione, citrate, L-cystathionine, and 4-pyridoxic acid, were significantly elevated following treatment, while N-acetylornithine and methylmalonate ester were decreased, indicating coordinated remodeling of oxidative stress defense, vitamin B6 homeostasis, and energy metabolism. Collectively, these findings indicate that Pedio6-1 not only possesses direct purine-degrading activity in vitro, but also ameliorates purine metabolic disturbances, inflammation, and oxidative stress in obese mice, likely through the modulation of porphyrin and amino acid metabolic pathways, highlighting its promise as a functional probiotic candidate for managing obesity-associated purine metabolic disorders.