Objective To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. Methods Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. Results The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). Conclusions The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(5): 550-560
Key words
Acute lymphoblastic leukemia /
Intestinal flora /
Chemotherapy /
Child
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References
1 Sánchez B, Delgado S, Blanco-Míguez A, et al. Probiotics, gut microbiota, and their influence on host health and disease[J]. Mol Nutr Food Res, 2017, 61(1): 1600240. PMID: 27500859. DOI: 10.1002/mnfr.201600240.
2 Bai L, Zhou P, Li D, et al. Changes in the gastrointestinal microbiota of children with acute lymphoblastic leukaemia and its association with antibiotics in the short term[J]. J Med Microbiol, 2017, 66(9): 1297-1307. PMID: 28855025. DOI: 10.1099/jmm.0.000568.
3 Lloyd-Price J, Arze C, Ananthakrishnan AN, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases[J]. Nature, 2019, 569(7758): 655-662. PMID: 31142855. PMCID: PMC6650278. DOI: 10.1038/s41586-019-1237-9.
4 Di Paola M, Cavalieri D, Albanese D, et al. Alteration of fecal microbiota profiles in juvenile idiopathic arthritis. associations with HLA-B27 allele and disease status[J]. Front Microbiol, 2016, 7: 1703. PMID: 27833598. PMCID: PMC5080347. DOI: 10.3389/fmicb.2016.01703.
5 Rajagopala SV, Singh H, Yu Y, et al. Persistent gut microbial dysbiosis in children with acute lymphoblastic leukemia (ALL) during chemotherapy[J]. Microb Ecol, 2020, 79(4): 1034-1043. PMID: 31754744. DOI: 10.1007/s00248-019-01448-x.
6 Gao X, Miao R, Zhu Y, et al. A new insight into acute lymphoblastic leukemia in children: influences of changed intestinal microfloras[J]. BMC Pediatr, 2020, 20(1): 290. PMID: 32522199. PMCID: PMC7646195. DOI: 10.1186/s12887-020-02192-9.
7 Chua LL, Rajasuriar R, Lim YAL, et al. Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy[J]. BMC Cancer, 2020, 20(1): 151. PMID: 32093640. PMCID: PMC7041273. DOI: 10.1186/s12885-020-6654-5.
8 中华医学会儿科学分会血液学组, 《中华儿科杂志》编辑委员会. 儿童急性淋巴细胞白血病诊疗建议(第四次修订)[J]. 中华儿科杂志, 2014, 52(9): 641-644. PMID: 25476423. DOI: 10.3760/cma.j.issn.0578-1310.2014.09.001.
9 Stary J, Zimmermann M, Campbell M, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002[J]. J Clin Oncol, 2014, 32(3): 174-184. PMID: 24344215. DOI: 10.1200/JCO.2013.48.6522.
10 Zwielehner J, Lassl C, Hippe B, et al. Changes in human fecal microbiota due to chemotherapy analyzed by TaqMan-PCR, 454 sequencing and PCR-DGGE fingerprinting[J]. PLoS One, 2011, 6(12): e28654. PMID: 22194876. PMCID: PMC3237468. DOI: 10.1371/journal.pone.0028654.
11 Yang J, Liu KX, Qu JM, et al. The changes induced by cyclophosphamide in intestinal barrier and microflora in mice[J]. Eur J Pharmacol, 2013, 714(1-3): 120-124. PMID: 23791611. DOI: 10.1016/j.ejphar.2013.06.006.
12 Hakim H, Dallas R, Wolf J, et al. Gut microbiome composition predicts infection risk during chemotherapy in children with acute lymphoblastic leukemia[J]. Clin Infect Dis, 2018, 67(4): 541-548. PMID: 29518185. PMCID: PMC6070042. DOI: 10.1093/cid/ciy153.
13 Lopez-Siles M, Duncan SH, Garcia-Gil LJ, et al. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics[J]. ISME J, 2017, 11(4): 841-852. PMID: 28045459. PMCID: PMC5364359. DOI: 10.1038/ismej.2016.176.
14 Hidalgo-Cantabrana C, Delgado S, Ruiz L, et al. Bifidobacteria and their health-promoting effects[J]. Microbiol Spectr, 2017, 5(3): BAD-0010-2016. PMID: 28643627. DOI: 10.1128/microbiolspec.BAD-0010-2016.
15 Gracie DJ, Guthrie EA, Hamlin PJ, et al. Bi-directionality of brain-gut interactions in patients with inflammatory bowel disease[J]. Gastroenterology, 2018, 154(6): 1635-1646.e3. PMID: 29366841. DOI: 10.1053/j.gastro.2018.01.027.
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