Leelahavanichkul Asada, Phuengmaung Pornpimol, Bhunyakarnjanarat Thansita, Kaewduangduen Warerat, Boonnaj Pimmada, Tengamnuay Pichanan, Chancharoenthana Wiwat, Tungsanga Somkanya, Udomkarnjananun Suwasin, Tumwasorn Somying
Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence on Translational Research in Inflammation and Immunology (CETRII) , Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2025 Jul 31;15(1):27990. doi: 10.1038/s41598-025-12768-z.
Because of the strain-dependent effect and the lack of simultaneous in vitro test with limited clinical data on Lacticaseibacillus rhamnosus L34 (L34) isolated from the Thai population, L34 was tested and compared with L. rhamnosus GG (LGG). The before and after test using L34 and a randomized placebo-controlled trial using placebo, L34, and LGG, for 4 weeks in patients with non-dialysis chronic kidney disease stage 3-5 (CKD) together with the in vitro experiments using indoxyl sulfate (IS, a representative uremic toxin) were performed. In comparison with the baseline, 4-week-L34 administration reduced gut-derived uremic toxins (GDUTs), except total IS, and attenuated several biomarkers, including i) systemic inflammation, as measured by cytokines and neutrophil extracellular traps using citrullinated histone 3, cell-free DNA, and fluorescent-stained nuclear morphology; ii) gut permeability defect (beta-D-glucan but not by endotoxemia); and iii) gut dysbiosis (fecal microbiome analysis). Additionally, L34-conditioned media attenuated IS-induced injuries on Caco-2 enterocytes, THP-1-derived-macrophages, and isolated neutrophils. Despite the possible different active compounds, both probiotics similarly attenuated IS-induced inflammation in vitro and in patients when compared with the placebo. In conclusion, L34 and LGG similarly attenuated systemic inflammation in patients with CKD, through the improved gut dysbiosis and anti-inflammation.
由于存在菌株依赖性效应，且从泰国人群中分离出的鼠李糖乳杆菌L34（L34）缺乏同时进行的体外试验及有限的临床数据，因此对L34进行了测试并与鼠李糖乳杆菌GG（LGG）进行比较。对非透析慢性肾脏病3 - 5期（CKD）患者进行了使用L34的测试前后对比试验以及一项使用安慰剂、L34和LGG的随机安慰剂对照试验，为期4周，同时还进行了使用硫酸吲哚酚（IS，一种代表性的尿毒症毒素）的体外实验。与基线相比，给予L34 4周可降低肠道源性尿毒症毒素（GDUTs），总IS除外，并减弱了几种生物标志物，包括：i）全身炎症，通过使用瓜氨酸化组蛋白3、游离DNA和荧光染色核形态的细胞因子和中性粒细胞胞外陷阱来测量；ii）肠道通透性缺陷（β - D - 葡聚糖而非内毒素血症）；以及iii）肠道菌群失调（粪便微生物组分析）。此外，L34条件培养基减轻了IS对Caco - 2肠上皮细胞、THP - 1衍生巨噬细胞和分离的中性粒细胞的损伤。尽管可能存在不同的活性化合物，但与安慰剂相比，这两种益生菌在体外和患者体内均同样减轻了IS诱导的炎症。总之，L34和LGG通过改善肠道菌群失调和抗炎作用，同样减轻了CKD患者的全身炎症。
