抗生素相关性中性粒细胞减少症的特点是儿科患者肠道中的拉赫诺斯皮拉菌大量减少

Josaura Fernandez-Sanchez, Rachel Rodgers, Arushana A. Maknojia, Nusrat Shaikh, Hannah Yan, Marlyd E. Mejia, Hope Hendricks, Robert R. Jenq, Pavan Reddy, Ritu Banerjee, Jeremy M. Schraw, Megan T. Baldridge, Katherine Y. King
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引用次数: 0

摘要

多达 34% 的患者在长期接触抗生素后会出现血液学副作用。据报道,10%-15% 的患者会出现中性粒细胞减少症,这增加了败血症和死亡的风险。小鼠研究已证实肠道微生物群与正常造血之间存在联系。我们试图找出在长期使用抗生素后出现中性粒细胞减少症的健康儿科患者的诱发因素、微生物群衍生代谢产物的存在以及肠道微生物群组成的变化。在这项多中心研究中,研究人员招募了预计需要接受两周或两周以上抗生素治疗的感染患者。我们在抗生素治疗开始和结束以及中性粒细胞减少时采集了粪便样本。我们确定了 10 名服用抗生素后出现中性粒细胞减少症的患者和 29 名年龄、性别、种族和民族相匹配的对照组。临床数据显示,中性粒细胞减少症与感染类型或使用的抗生素类型无关;但入住重症监护室和治疗时间长短与中性粒细胞减少症有关。肠道微生物组丰富度的降低和Lachnospiraceae家族成员丰度的降低与中性粒细胞减少症有关。非靶向粪便代谢组学分析显示,中性粒细胞减少症患者体内有几种代谢物被完全消耗,其中包括已知由拉氏螺旋藻产生的尿素循环途径、嘧啶代谢和脂肪酸代谢的成员。我们的研究证实了肠道微生物群紊乱与异常造血之间的关系,并确定了可能有助于微生物群持续造血的类群和代谢物。由于微生物群是干细胞移植和免疫疗法结果的关键决定因素,这些发现可能具有广泛意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antibiotic-associated neutropenia is marked by depletion of intestinal Lachnospiraceae in pediatric patients
Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance.
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