Han Wen-Bei, Liu Ying-Lu, Wan Yi-Gang, Sun Wei, Tu Yue, Yang Jing-Jing, Wu Wei, He Wei-Ming, Yao Jian
Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Chinese Medicine and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.
Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Zhongguo Zhong Yao Za Zhi. 2017 Jul;42(13):2425-2432. doi: 10.19540/j.cnki.cjcmm.20170609.014.
The gut microbiota dysbiosis is one of the risk factors in the progression from the advanced chronic kidney disease（CKD）to uremia, characterized by the reduction of probiotics and the increase of opportunistic pathogens including urease-related microbes, endotoxin-related microbes and toxin-related microbes, which can produce uremic toxins. According to the core point of "the gut-kidney axis" theory and "the chronic kidney disease-colonic axis" concept, the gut microbiota dysbiosis aggravates renal damage by accumulating uremic toxins and inducing the systemic micro-inflammation. The preliminary clinical trials and animal experiments show that the probiotics biologicals from Lactobacillus acidophilus or Bifidobacterium, and the prebiotics including inulin and galactooligosaccharides, as well as lubiprostone and activated carbon adsorbents can be used for improving dysfunction of CKD patients with the gut microbiota dysbiosis via reducing uremic toxins and inhibiting the systemic micro-inflammation. But not only that, it is reported that, to some extent, a number of the single Chinese herbal medicine（CHM）, the CHM prescriptions and the CHM extracts（emodin, etc.）with oral or enema administration can also regulate the gut microbiota dysbiosis, protect the intestinal epithelial barrier, reduce uremic toxins accumulation and delay CKD progression. Thereinto, Dahuang Gancao Decoction（the concentrated granule TJ-84）, a classical CHM prescription of rhubarb, can ameliorate uremic toxins accumulation in the animal models with renal failure probably through targeting the gut-kidney axis triggered from gut microbiota, but not targeting the kidney. Based on these results, the interventional studies targeting the gut microbiota-related pathological factors such as tight junction proteins, helper T cells and regulatory T cells in the intestinal tract of the advanced CKD patients will become one of the key development directions in the future.
肠道微生物群失调是晚期慢性肾脏病（CKD）进展为尿毒症的危险因素之一，其特征是益生菌减少，包括脲酶相关微生物、内毒素相关微生物和毒素相关微生物在内的机会性病原体增加，这些病原体可产生尿毒症毒素。根据“肠-肾轴”理论的核心要点和“慢性肾脏病-结肠轴”概念，肠道微生物群失调通过积累尿毒症毒素和诱导全身微炎症来加重肾脏损伤。初步临床试验和动物实验表明，嗜酸乳杆菌或双歧杆菌来源的益生菌生物制剂、包括菊粉和低聚半乳糖在内的益生元，以及鲁比前列酮和活性炭吸附剂可用于改善肠道微生物群失调的CKD患者的功能障碍，方法是减少尿毒症毒素并抑制全身微炎症。但不仅如此，据报道，一些单味中药、中药方剂以及口服或灌肠给药的中药提取物（如大黄素等）在一定程度上也可以调节肠道微生物群失调，保护肠上皮屏障，减少尿毒症毒素积累并延缓CKD进展。其中，大黄甘草汤（浓缩颗粒TJ-84），一种经典的大黄中药方剂，可能通过靶向由肠道微生物群引发的肠-肾轴而非靶向肾脏来改善肾衰竭动物模型中的尿毒症毒素积累。基于这些结果，针对晚期CKD患者肠道中紧密连接蛋白、辅助性T细胞和调节性T细胞等肠道微生物群相关病理因素的干预研究将成为未来的关键发展方向之一。
