新型降尿酸益生菌筛选及其益生特性评价

Screening of novel uric acid-lowering probiotics and evaluation of their probiotic properties

摘要:

为了应对高尿酸血症这一日益严峻的健康问题，同时规避或弥补现有临床治疗方案的局限性，本研究通过大规模筛选结合实验室适应性进化获得具有高效降尿酸能力的嗜酸乳杆菌(Lactobacillus acidophilus)菌株D801，通过评价其体外降尿酸能力、胃肠道耐受能力、自聚集性、耐酸/耐胆盐能力和对抗生素的敏感性来探究其益生特性。嗜酸乳杆菌D801在体外对尿酸的降解率可达到(57.26±6.52)% (2.0 mmol/L尿酸环境)；对8种抗生素均不具备耐药性；聚集率高达97.62% (3 h)；在pH 2.0和3.0条件下培养3 h的存活率分别为：(20.83±6.51)%和(50.00±16.24)%；能够耐受0.48% (质量体积分数)的牛胆盐浓度，3 h后活菌数仍能够达到4.0×10⁶ CFU/mL；在人工胃模拟液和肠模拟液3 h后的存活率分别为(102.8±15.56)%和(105.1±3.07)%；对于高尿酸血症小鼠，嗜酸乳杆菌D801能够降低20.65%血清尿酸，对小鼠肝脏和血清中的黄嘌呤氧化酶活性抑制率分别为36.24%和13.54%，脾体比降低17.09%，能够有效改善免疫系统，缓解机体炎症。本研究为高尿酸血症提供了一种更安全的干预手段。

Abstract:

To address the growing health challenge of hyperuricemia while circumventing or compensating for the limitations of existing clinical treatment options, through a combination of large-scale screening and laboratory-based adaptive evolution, we identified a Lactobacillus acidophilus strain D801 exhibiting robust capacity for uric acid degradation. We then systematically evaluated the probiotic properties of the strain by assessing the in vitro uric acid degradation capacity, gastrointestinal tolerance, auto-aggregation ability, acid and bile salt tolerance, and antibiotic susceptibility. Strain D801 demonstrated a degradation rate of (57.26± 6.52)% for 2.0 mmol/L uric acid in vitro. It exhibited no resistance to the eight tested antibiotics. Furthermore, it displayed strong auto-aggregation ability, with an aggregation rate reaching 97.62% after 3 hours of incubation. The strain maintained the survival rates of (20.83±6.51)% at pH 2.0 and (50.00±16.24)% at pH 3.0 following 3 h exposure. It tolerated up to 0.48% (W/V) sodium deoxycholate, retaining a viable count of 4.0×10⁶ CFU/mL after 3 h. In simulated gastric fluid and intestinal fluid, the strain maintained the survival rates at (102.8±15.56)% and (105.1±3.07)%, respectively. In vivo administration of L. acidophilus D801 significantly attenuated hyperuricemia in mice, reducing the serum uric acid level by 20.65%. Moreover, the strain decreased the xanthine oxidase (XOD) activity by 36.24% and 13.54% in the mouse liver and serum, respectively. Importantly, it reduced the spleen index by 17.09%. The results suggest that strain D801 improves the immune function and alleviates systemic inflammation. The core significance of this study lies in offering a safer approach for hyperuricemia.