Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
FASEB J. 2021 Nov;35(11):e21937. doi: 10.1096/fj.202100887RR.
Defective permeability barrier is considered to be an incentive of hyperuricemia, however, the link between them has not been proven. Here, we evaluated the potential preventive effects of Lactiplantibacillus plantarum N-1 (LPN1) on gut microbiota and intestinal barrier function in rats with hyperoxaluria-induced kidney stones. Male rats were supplied with 1% ethylene glycol (EG) dissolved in drinking water for 4 weeks to develop hyperoxaluria, and some of them were administered with LPN1 for 4 weeks before EG treatment as a preventive intervention. We found that EG not only resulted hyperoxaluria and kidney stone formation, but also promoted the intestinal inflammation, elevated intestinal permeability, and gut microbiota disorders. Supplementation of LPN1 inhibited the renal crystalline deposits through reducing urinary oxalic acid and renal osteopontin and CD44 expression and improved EG-induced intestinal inflammation and barrier function by decreasing the serum LPS and TLR4/NF-κB signaling and up-regulating tight junction Claudin-2 in the colon, as well as increasing the production of short-chain fatty acid (SCFAs) and the abundance of beneficial SCFAs-producing bacteria, mainly from the families of Lachnospiraceae and Ruminococcaceae. Probiotic LPN1 could prevent EG-induced hyperoxaluria by regulating gut microbiota and enhancing intestinal barrier function.
通透性屏障缺陷被认为是高尿酸血症的一个诱因,然而,它们之间的联系尚未得到证实。在这里,我们评估了植物乳杆菌 N-1(LPN1)对高草酸尿诱导肾结石大鼠肠道微生物群和肠道屏障功能的潜在预防作用。雄性大鼠饮用 1%乙二醇(EG)水溶液 4 周以产生高草酸尿症,其中一些大鼠在 EG 处理前用 LPN1 进行 4 周的预防性干预。我们发现 EG 不仅导致高草酸尿症和肾结石形成,还促进了肠道炎症、增加了肠道通透性和肠道微生物群紊乱。LPN1 的补充通过减少尿草酸和肾脏骨桥蛋白和 CD44 的表达抑制了肾脏结晶沉积,并通过降低血清 LPS 和 TLR4/NF-κB 信号以及上调结肠中的紧密连接 Claudin-2 来改善 EG 诱导的肠道炎症和屏障功能,同时增加短链脂肪酸(SCFA)的产生和有益的 SCFA 产生菌的丰度,主要来自lachnospiraceae 和 ruminococcaceae 科。益生菌 LPN1 可以通过调节肠道微生物群和增强肠道屏障功能来预防 EG 诱导的高草酸尿症。