Exploring the dynamics of gut microbiota, antibiotic resistance, and chemotherapy impact in acute leukemia patients: A comprehensive metagenomic analysis.

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Virulence Pub Date : 2024-12-01 Epub Date: 2024-12-02 DOI:10.1080/21505594.2024.2428843
Ying Luo, Taha Majid Mahmood Sheikh, Xin Li, YuMeng Yuan, Fen Yao, Meimei Wang, Xiaoling Guo, Jilong Wu, Muhammad Shafiq, Qingdong Xie, Xiaoyang Jiao
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Abstract

Leukemia poses significant challenges to its treatment, and understanding its complex pathogenesis is crucial. This study used metagenomic sequencing to investigate the interplay between chemotherapy, gut microbiota, and antibiotic resistance in patients with acute leukemia (AL). Pre- and post-chemotherapy stool samples from patients revealed alterations in microbial richness, taxa, and antibiotic resistance genes (ARGs). The analysis revealed a decreased alpha diversity, increased dispersion in post-chemotherapy samples, and changes in the abundance of specific bacteria. Key bacteria such as Enterococcus, Klebsiella, and Escherichia coli have been identified as prevalent ARG carriers. Correlation analysis between gut microbiota and blood indicators revealed potential links between microbial species and inflammatory biomarkers, including C-reactive protein (CRP) and adenosine deaminase (ADA). This study investigated the impact of antibiotic dosage on microbiota and ARGs, revealing networks connecting co-occurring ARGs with microbial species (179 nodes, 206 edges), and networks associated with ARGs and antibiotic dosages (50 nodes, 50 edges). Antibiotics such as cephamycin and sulfonamide led to multidrug-resistant Klebsiella colonization. Our analyses revealed distinct microbial profiles with Salmonella enterica elevated post-chemotherapy in NF patients and Akkermansia muciniphila elevated pre-chemotherapy. These microbial signatures could inform strategies to modulate the gut microbiome, potentially mitigating the risk of neutropenic fever in patients undergoing chemotherapy. Finally, a comprehensive analysis of KEGG modules shed light on disrupted metabolic pathways after chemotherapy, providing insights into potential targets for managing side effects. Overall, this study revealed intricate relationships between gut microbiota, chemotherapy, and antibiotic resistance, providing new insights into improving therapy and enhancing patient outcomes.

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探索急性白血病患者肠道微生物群、抗生素耐药性和化疗影响的动态:一项全面的宏基因组分析。
白血病对其治疗提出了重大挑战,了解其复杂的发病机制至关重要。本研究利用宏基因组测序研究急性白血病(AL)患者化疗、肠道微生物群和抗生素耐药性之间的相互作用。化疗前和化疗后患者粪便样本显示微生物丰富度、分类群和抗生素耐药基因(ARGs)的变化。分析显示α多样性降低,化疗后样品的分散度增加,特定细菌的丰度发生变化。肠球菌、克雷伯氏菌和大肠杆菌等关键细菌已被确定为ARG的普遍携带者。肠道微生物群与血液指标的相关性分析揭示了微生物物种与炎症生物标志物(包括c反应蛋白(CRP)和腺苷脱氨酶(ADA))之间的潜在联系。本研究调查了抗生素剂量对微生物群和ARGs的影响,揭示了共同发生的ARGs与微生物物种之间的网络(179个节点,206条边),以及与ARGs和抗生素剂量相关的网络(50个节点,50条边)。抗生素如头孢霉素和磺胺导致多重耐药克雷伯氏菌定植。我们的分析揭示了不同的微生物谱:NF患者化疗后肠沙门氏菌升高,化疗前嗜粘液阿克曼氏菌升高。这些微生物特征可以为调节肠道微生物组的策略提供信息,潜在地减轻化疗患者中性粒细胞减少热的风险。最后,对KEGG模块的全面分析揭示了化疗后被破坏的代谢途径,为管理副作用的潜在靶点提供了见解。总的来说,这项研究揭示了肠道微生物群、化疗和抗生素耐药性之间的复杂关系,为改善治疗和提高患者预后提供了新的见解。
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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
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