小柯机器人

中南大学周文等研究人员合作发现，靶向肠道微生物的氮循环和细胞对铵的吸收可改善多发性骨髓瘤患者对硼替佐米的耐药性。2023年12月18日，《细胞—代谢》杂志在线发表了这项成果。

研究人员表示，肠道微生物组被发现在多发性骨髓瘤（MM）的治疗中起着至关重要的作用，由于耐药性，MM至今仍被认为是不治之症。在之前的研究中，研究人员证实了MM患者体内富含肠道氮回收菌。然而，它们在MM复发中的作用仍不清楚。

研究人员强调了复发MM患者体内富集的弗氏柠檬酸杆菌（C. freundii）。通过粪便微生物移植实验，研究人员证明了C. freundii通过增加循环中的铵水平在诱导MM耐药性方面起着关键作用。铵通过跨膜通道蛋白SLC12A2进入MM细胞，通过稳定NEK2蛋白促进染色体不稳定性和耐药性。研究表明，呋塞米钠能下调SLC12A2，从而抑制MM细胞对铵盐的吸收，改善无进展生存期和疗效评分。这些发现为干预MM的进展和耐药性提供了新的治疗靶点和策略。

附：英文原文

Title: Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma

Author: Yinghong Zhu, Xingxing Jian, Shuping Chen, Gang An, Duanfeng Jiang, Qin Yang, Jingyu Zhang, Jian Hu, Yi Qiu, Xiangling Feng, Jiaojiao Guo, Xun Chen, Zhengjiang Li, Ruiqi Zhou, Cong Hu, Nihan He, Fangming Shi, Siqing Huang, Hong Liu, Xin Li, Lu Xie, Yan Zhu, Lia Zhao, Yichuan Jiang, Jian Li, Jinuo Wang, Lugui Qiu, Xiang Chen, Wei Jia, Yanjuan He, Wen Zhou

Issue&Volume: 2023-12-18

Abstract: The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.

DOI: 10.1016/j.cmet.2023.11.019

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00450-3

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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