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他克莫司 1

代谢组学 1

移植后糖尿病 1

红基因组学 1

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Mycophenolate mofetil or tacrolimus compared with azathioprine in long-term maintenance treatment for

《医学前沿（英文）》 2022年第16卷第5期页码 799-807 doi: 10.1007/s11684-021-0849-2

摘要： This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.

关键词： lupus nephritis mycophenolate mofetil tacrolimus maintenance therapy

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Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

《医学前沿（英文）》 2019年第13卷第4期页码 471-481 doi: 10.1007/s11684-019-0686-8

摘要： Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus . Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

关键词： antibiotics tacrolimus glucose disorders microbiome

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肝脏移植术后糖尿病患者肠道微生物组的变化 Article

凌琪, 韩玉秋, 马越, 王晓森, 朱铮, 王靖宇, 曹佳莹, 林笑含, 王军, 王保红

《工程（英文）》 2023年第31卷第12期页码 98-111 doi: 10.1016/j.eng.2023.09.006

摘要：

移植后糖尿病（PTDM）会增加肝移植（LT）受者移植失败和死亡的风险。实验研究表明免疫抑制性他克莫司（TAC）介导的肠道生态失调可能导致血糖紊乱，但仍尚未见相关临床研究报道。因此，本研究通过高通量鸟枪法宏基因组测序和代谢组学分析相结合的方法，对PTDM和非PTDM的肝脏移植受者队列中的肠道微生物组（IM）进行了表征，并破译了IM、TAC剂量和PTDM之间的潜在关联。通过与非 PTDM 和经典II型糖尿病（T2DM）进行对比分析，确定了PTDM患者的肠道微生物组代表性特征为：变形菌门富集和拟杆菌门减少。有趣的是，与改变的微生物代谢产物相一致，这些微生物在PTDM患者中的丰都变化与TAC的剂量显著关联。具体来说，与低TAC 谷浓度（< 5 ng∙mL^–1）的移植受体相比较，高 TAC 谷浓度（> 5 ng∙mL^–1）移植受者中的有益微生物水平被显著降低；同时，通过检测粪便代谢物发现其中参与α-亚麻酸和花生四烯酸-这些降低糖尿病发生的有益代谢物的显著降低。更进一步，这些微生物标签分子的变化与移植受者的血糖紊乱程度显著有关。总之，PTDM患者的粪便微生物组和代谢组发生了显著变化，且与 TAC 剂量相关。这项研究是首个探索PTDM患者的细菌分类学组成变化和细菌基因功能变化，以更好地理解IM对PTDM的影响。

关键词：移植后糖尿病他克莫司红基因组学代谢组学