Summary of studies evaluating the GM during chemotherapy in pediatric patients with AL
| Study . | Year . | Patients, n . | Leukemia type . | Type of analysis . | Sample site . | Main results . |
|---|---|---|---|---|---|---|
| Van Vliet et al25 | 2009 | 9 | AML | PCR denaturing gradient gel electrophoresis fingerprinting. FISH with specific bacterial oligonucleotide probes in order to quantify fecal bacteria. | Fecal samples | Reduction in the total number of bacteria; mainly anaerobic bacteria decreased, with a slight increase in enterococci. |
| Tunyapanit et al40 | 2018 | 87 | ALL/lymphoma | MICs according to the E-test. | Rectal swabs | Increased rate of E coli and K pneumoniae resistant to ciprofloxacin in patients receiving ciprofloxacin prophylaxis, with an increase in the MIC50 of ceftazidime. |
| Hakim et al23 | 2018 | 199 | ALL | V1-V3 16S rRNA gene sequencing | Fecal samples | Reduction of GM diversity (according to the Chao1, Shannon, and Simpson indices). Relative abundances of Bacteroidetes decreased, whereas Clostridiaceae and Streptococcaceae increased. Baseline GM with greater relative abundance of Proteobacteria predicted the development of febrile neutropenia. Enterococcaceae dominance during chemotherapy predicted febrile neutropenia and diarrheal illness, whereas Streptococcaceae dominance predicted diarrheal illness. |
| Nearing et al30 | 2019 | 16 | ALL | V4-V5 16S rRNA gene sequencing and metagenomic shotgun sequencing | Fecal samples | Differences in alpha (according to the Shannon index, evenness, number of observed amplicon sequence variants, and Faith’s phylogenetic diversity) and beta diversity (according to weighted UniFrac distances) between samples from patients with infectious complications and those without. Increased relative abundances of Proteobacteria and opportunistic pathogens, decrease in Bacteroidetes and F prausnitzii in patients with infectious complications, and increase in aerobic respiration pathways. |
| Chua et al16 | 2020 | 7 (+7 healthy controls) | ALL | V4 16S rRNA gene sequencing | Anal swabs | Relative abundance of Bacteroides and alpha diversity (according to the Chao 1 and Shannon indices) decreased. Restitution of diversity, but not composition, occurred after the cessation of chemotherapy. |
| Rajagopala et al24 | 2020 | 32 (+25 healthy siblings) | ALL | V4 16S rRNA gene sequencing | Fecal samples | GM richness (based on the Chao 1 index) and evenness (based on the Shannon index) during treatment were lower than those of healthy controls. Increased relative abundances of the mucolytic bacteria R gnavus and R torques. |
| De Pietri et al32 | 2020 | 51 | ALL | V3-V4 16S rRNA gene sequencing | Fecal samples | During induction, a low number of alpha-diversity variants (according to the number of observed amplicon sequence variants and the Shannon index) and an increased abundance of Enterococcus spp. associated with high levels of CRP and low plasma citrulline. High abundance of Lachnospiraceae spp. associated with increased citrulline and reduced CRP levels. |
| Study . | Year . | Patients, n . | Leukemia type . | Type of analysis . | Sample site . | Main results . |
|---|---|---|---|---|---|---|
| Van Vliet et al25 | 2009 | 9 | AML | PCR denaturing gradient gel electrophoresis fingerprinting. FISH with specific bacterial oligonucleotide probes in order to quantify fecal bacteria. | Fecal samples | Reduction in the total number of bacteria; mainly anaerobic bacteria decreased, with a slight increase in enterococci. |
| Tunyapanit et al40 | 2018 | 87 | ALL/lymphoma | MICs according to the E-test. | Rectal swabs | Increased rate of E coli and K pneumoniae resistant to ciprofloxacin in patients receiving ciprofloxacin prophylaxis, with an increase in the MIC50 of ceftazidime. |
| Hakim et al23 | 2018 | 199 | ALL | V1-V3 16S rRNA gene sequencing | Fecal samples | Reduction of GM diversity (according to the Chao1, Shannon, and Simpson indices). Relative abundances of Bacteroidetes decreased, whereas Clostridiaceae and Streptococcaceae increased. Baseline GM with greater relative abundance of Proteobacteria predicted the development of febrile neutropenia. Enterococcaceae dominance during chemotherapy predicted febrile neutropenia and diarrheal illness, whereas Streptococcaceae dominance predicted diarrheal illness. |
| Nearing et al30 | 2019 | 16 | ALL | V4-V5 16S rRNA gene sequencing and metagenomic shotgun sequencing | Fecal samples | Differences in alpha (according to the Shannon index, evenness, number of observed amplicon sequence variants, and Faith’s phylogenetic diversity) and beta diversity (according to weighted UniFrac distances) between samples from patients with infectious complications and those without. Increased relative abundances of Proteobacteria and opportunistic pathogens, decrease in Bacteroidetes and F prausnitzii in patients with infectious complications, and increase in aerobic respiration pathways. |
| Chua et al16 | 2020 | 7 (+7 healthy controls) | ALL | V4 16S rRNA gene sequencing | Anal swabs | Relative abundance of Bacteroides and alpha diversity (according to the Chao 1 and Shannon indices) decreased. Restitution of diversity, but not composition, occurred after the cessation of chemotherapy. |
| Rajagopala et al24 | 2020 | 32 (+25 healthy siblings) | ALL | V4 16S rRNA gene sequencing | Fecal samples | GM richness (based on the Chao 1 index) and evenness (based on the Shannon index) during treatment were lower than those of healthy controls. Increased relative abundances of the mucolytic bacteria R gnavus and R torques. |
| De Pietri et al32 | 2020 | 51 | ALL | V3-V4 16S rRNA gene sequencing | Fecal samples | During induction, a low number of alpha-diversity variants (according to the number of observed amplicon sequence variants and the Shannon index) and an increased abundance of Enterococcus spp. associated with high levels of CRP and low plasma citrulline. High abundance of Lachnospiraceae spp. associated with increased citrulline and reduced CRP levels. |
As for alpha diversity, the following metrics were used: the Shannon index (accounting for both abundance and evenness of the species present), the Chao 1 index (taking into account, besides species richness, the ratio of singletons to doubletons, giving more weight to rare species), the number of observed amplicon sequence variants (estimating the total species richness by counting the number of exact sequence variants down to the level of single-nucleotide differences), evenness (quantifying how numerically the community is equal), the Simpson index (accounting for both abundance and evenness of the species present but giving more weight to evenness and common or dominant species), and Faith’s phylogenetic diversity (the sum of the branch lengths of a phylogenetic tree connecting all species, thus reflecting the overall evolutionary history of divergence of a set of taxa).
AML, acute myeloid leukemia; FISH, fluorescence in situ hybridization; PCR, polymerase chain reaction.