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儿童急性淋巴细胞白血病患儿在化疗开始前、化疗期间和化疗停止后肠道微生物群特征的时间变化。

Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy.

机构信息

Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

BMC Cancer. 2020 Feb 24;20(1):151. doi: 10.1186/s12885-020-6654-5.

Abstract

BACKGROUND

Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.

METHODOLOGY

We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.

RESULTS

Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.

CONCLUSION

Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

摘要

背景

肠道微生物群的改变最近与儿童白血病和化疗的使用有关。在疾病缓解和癌症治疗停止后,失调的微生物群落是否得到恢复尚未得到评估。本研究检查了急性淋巴细胞白血病(ALL)患儿在化疗开始前、期间和停止后的肠道微生物群的时间变化。

方法

我们使用 16S 核糖体 RNA 测序对一组诊断为 ALL 的儿科患者的肠道微生物组进行了纵向观察研究,并将这些患者的微生物组模式与年龄和种族匹配的健康儿童进行了比较。还检查了 ALL 患者在不同化疗时间点的肠道微生物群的时间变化。

结果

在开始化疗之前,与健康对照组相比,ALL 患儿的肠道微生物群个体间变异性更大,并且富含厚壁菌门和拟杆菌属的细菌。在开始化疗时,拟杆菌的相对丰度下降。化疗停止后,肠道微生物群组成恢复到类似于健康对照组的状态。然而,尽管完成了化疗并假定恢复了正常健康,微生物群组成(β多样性)仍然存在差异,并且一些细菌在 ALL 患者中的丰度与对照组不同。

结论

本研究的初步结果首次表明,即使在化疗停止后,ALL 患儿的肠道微生物群图谱仍与健康对照组略有不同。这些持续的微生物变化可能与儿童癌症幸存者的长期健康有关,但这些变化对这些幸存者随后的健康影响仍有待探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d5/7041273/f6b173ba5a75/12885_2020_6654_Fig1_HTML.jpg

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