Departamento de Ciências Médicas, Universidade de Aveiro, Aveiro, Portugal; I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Int J Pharm. 2020 Jun 30;584:119450. doi: 10.1016/j.ijpharm.2020.119450. Epub 2020 May 26.
The progressive loss of renal function in chronic kidney disease (CKD) leads to the accumulation of uremic toxins. Recent studies related uremic plasma as well dysbiotic gut microbiome to impaired intestinal barrier function, allowing the translocation of microorganisms or by-products from the intestinal lumen to systemic circulation, contributing to systemic inflammation, cardiovascular risk and progression of CKD. Our main goal was to evaluate the impact of different uremic conditions on an improved in vitro intestinal Caco-2/HT29-MTX/Raji B triple co-culture model. For that, the impact of CKD patients' plasma and elevated urea concentration and its by-products on the triple model was assessed. The results showed that uremic conditions did not potentiate the Escherichia coli (E. coli) translocation, although may interfere with the integrity and the permeability of the intestinal barrier. Also, results showed that E. coli translocation was higher in Caco-2 monoculture than in Caco-2/HT29-MTX/Raji B triple model, suggesting that the triple model creates a more effective intestinal barrier. This study allowed to conclude that the uremic state influences the integrity of the intestinal barrier, but this influence could not be directly translated in an increase on the E. coli translocation through the intestinal epithelium, at least in Caco-2/HT29-MTX/Raji B intestinal epithelial barrier model.
慢性肾脏病 (CKD) 中肾功能的逐渐丧失会导致尿毒症毒素的积累。最近的研究将尿毒症血浆以及肠道微生物失调与受损的肠道屏障功能相关联，使微生物或肠道腔室的副产物易位至全身循环，导致全身炎症、心血管风险和 CKD 的进展。我们的主要目标是评估不同尿毒症条件对改良的体外肠 Caco-2/HT29-MTX/Raji B 三重共培养模型的影响。为此，评估了 CKD 患者血浆和升高的尿素浓度及其副产物对三重模型的影响。结果表明，尿毒症条件并未增强大肠杆菌 (E. coli) 的易位，尽管可能干扰肠道屏障的完整性和通透性。此外，结果表明，E. coli 在 Caco-2 单层培养中的易位高于 Caco-2/HT29-MTX/Raji B 三重模型，表明三重模型可创建更有效的肠道屏障。这项研究的结论是，尿毒症状态会影响肠道屏障的完整性，但这种影响不能直接转化为通过肠道上皮细胞的 E. coli 易位增加，至少在 Caco-2/HT29-MTX/Raji B 肠道上皮屏障模型中是如此。
