Table 1.

Association between microbial diversity changes and outcomes of cellular therapy

TherapySampling sites Technology and pipeline FindingsReference
Human     
Auto-HCT US 16S
UPARSE 
Increased α-diversity in perineutrophil engraftment fecal samples is associated with increased OS and PFS 16  
US 16S
QIIME2 and DADA2 
Increased α-diversity in perineutrophil engraftment fecal samples is correlated with CR/VGPR vs PR 21  
US 16S
QIIME 
Increased α-diversity in posttransplant samples is correlated with less severe diarrhea; increased diversity is associated with the development of neutropenic fever. 26  
US 16S
DADA2 
Increased oral microbial α-diversity is correlated with higher salivary and serum melphalan levels 28  
Allo-HCT US 16S
Mothur 
Low baseline fecal α-diversity is associated with pulmonary complications 27  
France 16S
QIIME 
Decreased α-diversity in pretreatment fecal samples is associated with subsequent bacteremia 22  
Italy and Poland  16S
QIIME2 
Increased α-diversity in pretreatment fecal samples is associated with increased OS and lower grades of aGVHD 18  
US 16S
DADA2 
Increased α-diversity in periengraftment samples is associated with MAIT and Vδ2 T-cell frequency at day 30 in patients who received unmodified PBMC grafts 29  
US, Germany, and Japan 16S vsearch, usearch, and QIIME Increased α-diversity in periengraftment fecal samples is associated with increased OS and a lower transplantation-related mortality rate 19  
US 16S
DADA2 
Increased α-diversity in periengraftment fecal samples is associated with increased OS, decreased nonrelapse mortality, and better CD4 and CD8 T-cell recovery 17  
US 16S
DADA2 
Increased α-diversity in perineutrophil recovery fecal samples is associated with lower grades of aGVHD 24  
US Shotgun metagenomics
QIIME2 and vegan.R 
Patients who developed cGVHD showed a change of β-diversity and a greater loss of α-diversity from baseline to after engraftment 25  
US 16S
Mothur 
Increased α-diversity in postengraftment fecal samples is associated with increased OS and a lower transplantation-related mortality rate 20  
Auto-HCT/allo-HCT China 16S
QIIME and UPARSE 
Increased α-diversity in posttransplant samples is associated with decreased bacteremia 23  
CAR T cell China 16S
QIIME2 
α-Diversity is decreased in fecal samples from PR patients compared with fecal samples from CR patients at the CRS peak time point. β-Diversity is different between PR and CR samples at the same time point. 30  
Mouse     
Syngeneic BMT US 16S
Mothur 
Authors defined intestinal microbiota score = Shannon index × fecal bacterial abundance. Higher intestinal microbiota score is associated with higher weight of periovarian fat, bone marrow, and thymic cellularity after transplantation. 31  
Allo-HCT US 16S
Mothur 
Higher α-diversity in posttransplant samples is associated with better survival and lower GVHD score 32  
US 16S Orally gavaging B fragilis increases posttransplant α-diversity in the ileum, and ameliorates GVHD 33  
US 16S
QIIME2 and DADA2 
High vitamin A diet is associated with decreased α-diversity in posttransplant fecal samples and more severe lung GVHD 34  
Australia Metagenomics
QIIME 
Wild-type mice cohoused continuously with IL-17RA–deficient mice display decreased α-diversity and accelerated GVHD 35  
CAR T cell US 16S
QIIME2 
Oral vancomycin treatment decreased the α-diversity of fecal samples from mice with human FMT. CAR T-cell therapy in combination with vancomycin slowed down tumor progression. 36  
TherapySampling sites Technology and pipeline FindingsReference
Human     
Auto-HCT US 16S
UPARSE 
Increased α-diversity in perineutrophil engraftment fecal samples is associated with increased OS and PFS 16  
US 16S
QIIME2 and DADA2 
Increased α-diversity in perineutrophil engraftment fecal samples is correlated with CR/VGPR vs PR 21  
US 16S
QIIME 
Increased α-diversity in posttransplant samples is correlated with less severe diarrhea; increased diversity is associated with the development of neutropenic fever. 26  
US 16S
DADA2 
Increased oral microbial α-diversity is correlated with higher salivary and serum melphalan levels 28  
Allo-HCT US 16S
Mothur 
Low baseline fecal α-diversity is associated with pulmonary complications 27  
France 16S
QIIME 
Decreased α-diversity in pretreatment fecal samples is associated with subsequent bacteremia 22  
Italy and Poland  16S
QIIME2 
Increased α-diversity in pretreatment fecal samples is associated with increased OS and lower grades of aGVHD 18  
US 16S
DADA2 
Increased α-diversity in periengraftment samples is associated with MAIT and Vδ2 T-cell frequency at day 30 in patients who received unmodified PBMC grafts 29  
US, Germany, and Japan 16S vsearch, usearch, and QIIME Increased α-diversity in periengraftment fecal samples is associated with increased OS and a lower transplantation-related mortality rate 19  
US 16S
DADA2 
Increased α-diversity in periengraftment fecal samples is associated with increased OS, decreased nonrelapse mortality, and better CD4 and CD8 T-cell recovery 17  
US 16S
DADA2 
Increased α-diversity in perineutrophil recovery fecal samples is associated with lower grades of aGVHD 24  
US Shotgun metagenomics
QIIME2 and vegan.R 
Patients who developed cGVHD showed a change of β-diversity and a greater loss of α-diversity from baseline to after engraftment 25  
US 16S
Mothur 
Increased α-diversity in postengraftment fecal samples is associated with increased OS and a lower transplantation-related mortality rate 20  
Auto-HCT/allo-HCT China 16S
QIIME and UPARSE 
Increased α-diversity in posttransplant samples is associated with decreased bacteremia 23  
CAR T cell China 16S
QIIME2 
α-Diversity is decreased in fecal samples from PR patients compared with fecal samples from CR patients at the CRS peak time point. β-Diversity is different between PR and CR samples at the same time point. 30  
Mouse     
Syngeneic BMT US 16S
Mothur 
Authors defined intestinal microbiota score = Shannon index × fecal bacterial abundance. Higher intestinal microbiota score is associated with higher weight of periovarian fat, bone marrow, and thymic cellularity after transplantation. 31  
Allo-HCT US 16S
Mothur 
Higher α-diversity in posttransplant samples is associated with better survival and lower GVHD score 32  
US 16S Orally gavaging B fragilis increases posttransplant α-diversity in the ileum, and ameliorates GVHD 33  
US 16S
QIIME2 and DADA2 
High vitamin A diet is associated with decreased α-diversity in posttransplant fecal samples and more severe lung GVHD 34  
Australia Metagenomics
QIIME 
Wild-type mice cohoused continuously with IL-17RA–deficient mice display decreased α-diversity and accelerated GVHD 35  
CAR T cell US 16S
QIIME2 
Oral vancomycin treatment decreased the α-diversity of fecal samples from mice with human FMT. CAR T-cell therapy in combination with vancomycin slowed down tumor progression. 36  

BMT, bone marrow transplantation; cGVHD, chronic GVHD; CRS, cytokine release syndrome; IL-17RA, interleukin 17 receptor A; PBMC, peripheral blood mononuclear cell; PR, partial response; US, United States; VGPR, very good partial response.

Conclusions may vary based on the sampling site and methodology.

All human studies were performed in adult cohorts except this one in a pediatric cohort.

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