Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats.
Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats.
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糖肾方调节糖尿病肾病大鼠肠道微生物群并减少肠道源性毒素。
DOI：
10.1016/j.biopha.2020.110325
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发表时间：
2020-06
影响因子：
7.5
通讯作者：
Ping Li
中科院分区：
文献类型：
--
作者：
Tingting Zhao;Haojun Zhang;Xingbin Yin;Hailing Zhao;Liang Ma;Meihua Yan;Liang Peng;Qian Wang;Xi Dong;Ping Li
越来越多的证据表明，糖尿病肾病(DKD)与肠源性毒素引起的肠道生物失调有关。糖肾方(TSF)是一种用于治疗DKD的传统中草药。本研究通过建立链脲佐菌素注射和单肾切除诱导的糖尿病肾病大鼠模型，探讨TSF对糖尿病大鼠肠道微生物区系组成、肠源性毒素以及尿毒素在肾脏下游的炎症途径的影响。TSF治疗12周后，与未治疗的糖尿病肾病大鼠相比，肾脏组织学损伤和尿白蛋白排泄均明显减轻。TSF治疗还重建了肠道生态失调，降低了吲哚硫酸盐和代谢性内毒素血症/脂多糖的水平。血清和肾脏组织中单核细胞趋化蛋白-1和肿瘤坏死因子-α均显著降低。此外，我们还发现天花粉蛋白对肾脏炎症的抑制作用与抑制吲哚硫酸酯受体芳烃和TLR4有关，从而抑制了肾脏中的JNK和NF-κB信号转导。Spearman相关分析发现，肠道细菌门和属的聚集性与肾脏病理、肾功能和全身炎症显著相关。总之，口服TSF可显著抑制糖尿病大鼠肾脏损伤，并调节肠道微生物区系，从而降低内毒素和吲哚硫酸盐水平，减轻肾脏炎症。我们的结果表明，TSF可作为预防糖尿病肾病患者肠道菌群失调和清除肠道毒素的药物。
Growing evidence shows that diabetic kidney disease (DKD) is linked with intestinal dysbiosis from gut-derived toxins. Tangshen Formula (TSF) is a traditional Chinese herbal medicine that has been used to treat DKD. In this study, streptozotocin injection and uninephrectomy-induced diabetic nephropathy (DN) rat model was established to explore the impact of TSF on gut microbiota composition, gut-derived toxins, and the downstream inflammatory pathway of urotoxins in the kidney. TSF treatment for 12 weeks showed significant attenuation of both renal histologic injuries and urinary excretion of albumin compared with DN rats without treatment. TSF treatment also reconstructed gut dysbiosis and reduced levels of indoxyl sulfate and metabolic endotoxemia/lipopolysaccharide. MCP-1 and TNF-α were decreased by TSF both in the serum and kidney. In addition, we revealed that the inhibitory effect of TSF on renal inflammation was associated with the inhibition of aryl hydrocarbon, a receptor of indoxyl sulfate, and TLR4, thereby inhibiting JNK and NF-κB signaling in the kidney. Spearman correlation analysis found that a cluster of gut bacterial phyla and genera were significantly correlated with renal pathology, renal function, and systemic inflammation. In conclusion, orally administered TSF significantly inhibited diabetic renal injury, and modulated gut microbiota, which decreased levels of lipopolysaccharide and indoxyl sulfate, and attenuated renal inflammation. Our results indicate that TSF may be used as an agent in the prevention of gut dysbiosis and elimination of intestinal toxins in DN individuals.
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影响因子：
3.7
作者：
Zhao TT;Zhang HJ;Lu XG;Huang XR;Zhang WK;Wang H;Lan HY;Li P
通讯作者：
Li P
影响因子：
3.4
作者：
Tie Zhao;Haojun Zhang;Tingting Zhao;Xianglin Zhang;Jin-Jin Lu-Jin;Tingting Yin;Qiong-lin Liang;Yi-ming Wang;G. Luo;Huiyao Lan;Ping Li
通讯作者：
Tie Zhao;Haojun Zhang;Tingting Zhao;Xianglin Zhang;Jin-Jin Lu-Jin;Tingting Yin;Qiong-lin Liang;Yi-ming Wang;G. Luo;Huiyao Lan;Ping Li
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
5
作者：
Simeoni M;Citraro ML;Cerantonio A;Deodato F;Provenzano M;Cianfrone P;Capria M;Corrado S;Libri E;Comi A;Pujia A;Abenavoli L;Andreucci M;Cocchi M;Montalcini T;Fuiano G
通讯作者：
Fuiano G
影响因子：
30.3
作者：
Devlin AS;Marcobal A;Dodd D;Nayfach S;Plummer N;Meyer T;Pollard KS;Sonnenburg JL;Fischbach MA
通讯作者：
Fischbach MA