Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection.

IF 4.6 2区医学 Q1 MICROBIOLOGY Annals of Clinical Microbiology and Antimicrobials Pub Date : 2024-06-15 DOI:10.1186/s12941-024-00717-z

Huidi Wang, Yajie Zhang, Qianyi Zhou, Lihua Yu, Jingxiang Fu, Danna Lin, Lulu Huang, Xiaorong Lai, Li Wu, Jingxin Zhang, Juan Zi, Xu Liao, Siying Huang, Yugu Xie, Yan He, Lihua Yang

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Abstract

Background: Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown.

Methods: Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy.

Results: The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720.

Conclusions: Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy.

Trial registration: The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).

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急性淋巴细胞白血病患儿在诱导治疗期间的微生物元基因组变化以及感染的预测性生物标志物。

背景：新的证据表明，肠道微生物群与急性淋巴细胞白血病（ALL）之间存在联系。然而，化疗期间肠道微生物群的急性变化以及基线肠道微生物群对感染性并发症的预测价值在很大程度上仍然未知：方法：在化疗开始（基线，T0）、化疗开始后 7 天（T1）和化疗开始后 33 天（T2）三个时间点收集正在接受诱导化疗的 ALL 患儿（49 人）的粪便样本（126 份）。通过元基因组霰弹枪测序对肠道微生物组进行了分析。采用 bioBakery3 管道（Kneaddata、Metaphlan 3 和 HUMAnN）进行分类和功能注释。利用T0时的肠道微生物组预测化疗期间的感染情况：结果：化疗期间微生物的多样性和组成发生了显著变化，大肠埃希氏菌、肺炎克雷伯氏菌和长双歧杆菌是最主要的物种。化疗期间微生物的代谢途径也发生了明显变化，包括丙酮酸发酵至醋酸盐和乳酸盐的途径以及硫酸盐同化还原途径。基于T0时长双歧杆菌的接收者操作特征（ROC）模型可以预测化疗第一个月的感染并发症，其曲线下面积（AUC）为0.720：我们的研究为了解 ALL 患儿化疗期间微生物和功能特征的急性变化提供了新的视角。基线肠道微生物群可能是化疗期间感染的潜在生物标志物：本研究经南方医科大学珠江医院伦理委员会批准（2021-KY-171-01），并在http://www.chictr.org.cn（ChiCTR2200065406，注册日期：2022年11月4日）。

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来源期刊

Annals of Clinical Microbiology and Antimicrobials MICROBIOLOGY-

CiteScore

8.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.