Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical trials have been limited and inconclusive in determining the potential for microbially based interventions. Here, we used an established Drosophila melanogaster model of urolithiasis as a high-throughput screening platform for evaluation of the therapeutic potential of oxalate-degrading bacteria in calcium oxalate (CaOx) nephrolithiasis. The results demonstrated that Bacillus subtilis 168 (BS168) is a promising candidate based on its preferential growth in high oxalate concentrations, its ability to stably colonize the D. melanogaster intestinal tract for as long as 5 days, and its prevention of oxalate-induced microbiota dysbiosis. Single-dose BS168 supplementation exerted beneficial effects on D. melanogaster for as long as 14 days, decreasing stone burden in dissected Malpighian tubules and fecal excreta while increasing survival and behavioral markers of health over those of nonsupplemented lithogenic controls. These findings were complemented by in vitro experiments using the established MDCK renal cell line, which demonstrated that BS168 pretreatment prevented increased CaOx crystal adhesion and aggregation. Taking our results together, this study supports the notion that BS168 can functionally reduce CaOx stone burden in vivo through its capacity for oxalate degradation. Given the favorable safety profile of many B. subtilis strains already used as digestive aids and in fermented foods, these findings suggest that BS168 could represent a novel therapeutic adjunct to reduce the incidence of recurrent CaOx nephrolithiasis in high-risk patients.

中文翻译：

---

草酸盐降解枯草芽孢杆菌减轻黑腹果蝇模型中的尿石症。

肾结石影响了北美近 10% 的人口，并且与高发病率和复发率相关，但缺乏新的预防策略。最近的证据表明，人类肠道微生物群可以影响肾结石的发展，尽管临床试验在确定基于微生物的干预措施的潜力方面是有限的和不确定的。在这里，我们使用已建立的黑腹果蝇模型作为高通量筛选平台，用于评估草酸降解细菌在草酸钙 (CaOx) 肾结石中的治疗潜力。结果表明，枯草芽孢杆菌168 (BS168) 是一种很有前景的候选物，因为它在高草酸盐浓度下优先生长，能够在黑腹果蝇肠道中稳定定植长达 5 天，并能预防草酸盐引起的微生物群失调。单剂量 BS168 补充剂对黑腹果蝇产生了长达 14 天的有益影响，减少了解剖的 Malpighian 小管和粪便排泄物中的结石负担，同时增加了存活率和健康行为标志物，而不是未补充的岩性对照。这些发现得到了体外补充使用已建立的 MDCK 肾细胞系进行的实验表明，BS168 预处理可防止 CaOx 晶体粘附和聚集增加。综合我们的结果，这项研究支持 BS168 可以通过其草酸盐降解能力在功能上减少体内CaOx 结石负荷的观点。鉴于许多已经用作消化助剂和发酵食品的枯草芽孢杆菌菌株具有良好的安全性，这些发现表明 BS168 可以代表一种新的治疗辅助手段，以降低高危患者复发性 CaOx 肾结石的发生率。