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

Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy (VSports注册入口)

Ling Ling Chua  1   2 , Reena Rajasuriar  3   4 , Yvonne Ai Lian Lim  4   5 , Yin Ling Woo  2   4 , P'ng Loke  6 , Hany Ariffin  7   8
Affiliations

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

Ling Ling Chua et al. BMC Cancer. .

VSports app下载 - 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 VSports手机版. .

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 V体育安卓版. 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. V体育ios版.

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. VSports最新版本.

Keywords: Bacteroides; Bacteroidetes; Chemotherapy; Childhood acute lymphoblastic leukemia; Microbiome; Microbiota dysbiosis. V体育平台登录.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Beta diversity and alpha diversity measures of the ALL patients and controls samples. Bacterial beta diversity was measured with Bray-Curtis dissimilarity distances and visualised on NMDS plot. The samples were coloured according to sampling phase (pre-, during-, or post-chemo) or group (controls) and joined with the respective centroid (labelled with ‘C’). Pre-chemo sample was connected to the last sample Post-chemo with dotted arrow. PERMANOVA shows significant bacterial community differences among the groups (a). Bray-Curtis dissimilarity between the post-chemo samples (last timepoint) and controls was also compared (b). Microbiota dispersions were assessed based on distances from centroid (c). Shannon index and Chao1 index of the pre-chemo, during-chemo (average), post-chemo (last timepoint) samples of ALL patients and controls were also plotted on boxplots and comparison were made with Mann-Whitney tests (for unpaired samples) and Wilcoxon signed-rank test (for paired samples) (d, e)
Fig. 2
Fig. 2
Bacteria phyla compositions in ALL patients and healthy controls. Distribution of the most abundant phyla in each patient across sampling time (labelled as month from baseline) and sampling phase (pre-, during-, and post-chemotherapy), as well as in controls were visualized with stacked barplots (a). These top 6 phyla (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia) comprised more than 99% of the abundance, while other taxa were grouped as ‘other’. Average relative abundances of the phyla of the first (pre-chemo) and last (post-chemo) samples of the ALL patients, as well as the controls were also plotted on barplots (b). Comparison of the phyla relative abundances between pre-chemo, post-chemo and control groups identified three phyla (Bacteroidetes, Firmicutes and Actinobacteria) that were significantly different among the groups (c, d, e). The lower quartile relative abundance of Bacteroidetes and the higher quartile relative abundances of Firmicutes and Actinobacteria of the control group were indicated with dotted lines
Fig. 3
Fig. 3
Differentially abundant bacteria were identified between ALL patients and healthy controls. OTU abundances were normalized and compared using Deseq2 analysis pipeline. OTUs with log2 fold change (FC) > 4, base mean > 20 and FDR-adjusted q-values < 0.1 were considered significantly different. Comparison between pre-chemo and control groups identified 13 OTUs that were lower in abundances while 9 OTUs that were higher in abundances in the pre-chemo samples (a). Comparison between post-chemo and controls groups identified 5 OTUs that were lower in abundances while one OTU was higher in abundance in the post-chemo samples (b). The 9 OTUs that were most abundant among the pre-chemo samples belong to Bacteroides genus. Changes in relative abundance of Bacteroides genus in each ALL patient were tracked before, during and after cessation of chemotherapy (c)
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