Table 1.

Preclinical evidence: role of antibiotics in modulating microbiota and outcomes of HCT

AntibioticsModelMethodEffects on microbiomeOutcomesRef
Syngeneic 
Vancomycin, 0.5 g/L
Amikacin, 0.5 g/L 
B6 → B6 Fed water ad libitum from d –5 to the end of the experiment ↓ Colonic bacterial abundance ↓ Posttransplant hematopoiesis 12  
Ampicillin, 0.5 g/L
Enrofloxacin, 0.25 g/L 
B6 → B6 Fed water ad libitum from d –5 to the end of the experiment ↓ Colonic bacterial abundance ↓ Posttransplant hematopoiesis 12  
Vancomycin, 0.5 g/L
Neomycin, 1 g/L 
B6 T cells → NK-depleted RAG1–/– B6 Fed water ad libitum from d –7 to d 28 of transplant ↓ Microbial diversity
↓ Firmicutes
↑ Verrucomicrobia
↑ Proteobacteria
↓ Bacteroidetes
↓ Spirochaetes 
↓ BM cell number
↓ BM myeloid and NK cells
↓ Colonic inflammation 
13  
Bacitracin, 5 g/L
Neomycin, 2 g/L
Natamycin, 1.2 mg/L
Meropenem, 1 g/L
Vancomycin, 1 g/L 
B6 → B6 Fed water ad libitum from d 28 to d 42 of transplant ↓ Firmicutes
↓↓ Bacteroidetes
↑ Firmicutes to Bacteroidetes ratio
↑ Proteobacteria 
↑ BM-derived monocyte infiltration into the brain 14  
Allo-HCT 
Ampicillin, 5 mg
Metronidazole, 4 mg
Clindamycin, 5 mg
Vancomycin, 5 mg 
MHC-mismatched
B10.BR → B6 
Gavaged daily for 6 d before transplant ↓ Obligate anaerobes ↓ Survival 15  
Ampicillin, 250 mg/kg
Metronidazole, 250 mg/kg
Kanamycin, 250 mg/kg
Vancomycin, 125 mg/kg 
MHC-mismatched
BALB/c → B6 
Gavaged daily from d –1 to d 21 of transplant ↓ Bacteroidetes
↑ Proteobacteria 
↓ Survival 16  
Piperacillin-tazobactam, 100 mg/kg MHC-matched minor antigen–mismatched
B6 → 129S1 
Subcutaneous injected daily from d 10 to d 24 of transplant Near-complete gut-decontamination ↓ Survival  17  
Ampicillin, 200 μg
Gentamicin, 200 μg
Metronidazole, 200 μg
Kanamycin, 200 μg
Vancomycin, 100 μg 
MHC-mismatched
BALB/c → B6 
Gavaged daily from d 0 to d 5 of transplant ↓ Butyrate-producing Clostridiales species
↑ Non-butyrogenic genus Lactobacillus, phylum Proteobacteria 
↓ Survival 18  
Ampicillin, 0.5 g/L
Enrofloxacin, 0.25 g/L 
MHC-matched minor antigen–mismatched
129 → B6 
Fed water ad libitum from d –5 to the end of the experiment ↓ Colonic bacterial abundance ↓ Post-transplant hematopoiesis 12  
Vancomycin, 0.5 g/L
Neomycin, 1 g/L 
MHC-mismatched
BALB/c T cells → NK-depleted RAG1–/– B6 
Fed water ad libitum from d –7 to d 28 of transplant ↓ Microbial diversity
↓ Firmicutes
↑ Verrucomicrobia
↑ Proteobacteria
↓ Bacteroidetes 
↓ BM and spleen conventional T cells 13  
Imipenem/cilastatin, 100 mg/kg MHC-matched minor antigen–mismatched
B6 → 129S1 
Subcutaneous injected daily from d 10 to d 24 of transplant ↓ Clostridia,
↑ Verrucomicrobiales,
Akkermansia  
↓ Survival,
↑ GI GVHD,
↑ Donor CD4+ T cells, IL-23, and colonic granulocyte number  
17  
Imipenem/cilastatin, 50 mg/kg MHC-mismatched
B6 → BALB/c 
Gavaged daily from d –3 to d –1 of transplant ↑ Bacteroidaceae and Bacteroidales_S24-7_group,
↓ Porphyromonadaceae  
↓ Survival
↑ GVHD  
19  
Ampicillin, 1 g/L MHC-mismatched
B10.BR → B6 
Fed water ad libitum from d –21 to d –14 of transplant Lactobacillus
Blautia 
↓ Survival
↑ GI GVHD 
20  
Meropenem, 0.625 g/L MHC-mismatched
B6 → B6D2F1 
Fed water ad libitum from d 3 to d 15 of transplant ↓ Bacterial density
↓ α-diversity
↓ Clostridia
Bacteroides, Enterococcus, Erysipelatoclostridium, Bifidobacterium, and Akkermansia 
↓ Survival
↑ GI GVHD 
21  
Gentamicin, 0.5 g/L MHC-matched minor antigen–mismatched
B10.D2/nSnSlc → BALB/cCrSlc 
Orally administered from d –14 to d 28 of transplant Not mentioned ↓ cGVHD 22  
Polymyxin B, 100 mg/kg MHC-mismatched
B6 → B6D2F1 
Gavaged daily from d –4 to d 28 of transplant E coli ↑ Survival
↓ GVHD
↓ Donor T-cell expansion in the small intestine 
23  
Azithromycin, 100 mg/kg MHC-mismatched
B6 → BALB/c 
Gavaged daily from d –2 to d 2 of transplant Not mentioned ↑ Survival
↓ GVHD 
24  
AntibioticsModelMethodEffects on microbiomeOutcomesRef
Syngeneic 
Vancomycin, 0.5 g/L
Amikacin, 0.5 g/L 
B6 → B6 Fed water ad libitum from d –5 to the end of the experiment ↓ Colonic bacterial abundance ↓ Posttransplant hematopoiesis 12  
Ampicillin, 0.5 g/L
Enrofloxacin, 0.25 g/L 
B6 → B6 Fed water ad libitum from d –5 to the end of the experiment ↓ Colonic bacterial abundance ↓ Posttransplant hematopoiesis 12  
Vancomycin, 0.5 g/L
Neomycin, 1 g/L 
B6 T cells → NK-depleted RAG1–/– B6 Fed water ad libitum from d –7 to d 28 of transplant ↓ Microbial diversity
↓ Firmicutes
↑ Verrucomicrobia
↑ Proteobacteria
↓ Bacteroidetes
↓ Spirochaetes 
↓ BM cell number
↓ BM myeloid and NK cells
↓ Colonic inflammation 
13  
Bacitracin, 5 g/L
Neomycin, 2 g/L
Natamycin, 1.2 mg/L
Meropenem, 1 g/L
Vancomycin, 1 g/L 
B6 → B6 Fed water ad libitum from d 28 to d 42 of transplant ↓ Firmicutes
↓↓ Bacteroidetes
↑ Firmicutes to Bacteroidetes ratio
↑ Proteobacteria 
↑ BM-derived monocyte infiltration into the brain 14  
Allo-HCT 
Ampicillin, 5 mg
Metronidazole, 4 mg
Clindamycin, 5 mg
Vancomycin, 5 mg 
MHC-mismatched
B10.BR → B6 
Gavaged daily for 6 d before transplant ↓ Obligate anaerobes ↓ Survival 15  
Ampicillin, 250 mg/kg
Metronidazole, 250 mg/kg
Kanamycin, 250 mg/kg
Vancomycin, 125 mg/kg 
MHC-mismatched
BALB/c → B6 
Gavaged daily from d –1 to d 21 of transplant ↓ Bacteroidetes
↑ Proteobacteria 
↓ Survival 16  
Piperacillin-tazobactam, 100 mg/kg MHC-matched minor antigen–mismatched
B6 → 129S1 
Subcutaneous injected daily from d 10 to d 24 of transplant Near-complete gut-decontamination ↓ Survival  17  
Ampicillin, 200 μg
Gentamicin, 200 μg
Metronidazole, 200 μg
Kanamycin, 200 μg
Vancomycin, 100 μg 
MHC-mismatched
BALB/c → B6 
Gavaged daily from d 0 to d 5 of transplant ↓ Butyrate-producing Clostridiales species
↑ Non-butyrogenic genus Lactobacillus, phylum Proteobacteria 
↓ Survival 18  
Ampicillin, 0.5 g/L
Enrofloxacin, 0.25 g/L 
MHC-matched minor antigen–mismatched
129 → B6 
Fed water ad libitum from d –5 to the end of the experiment ↓ Colonic bacterial abundance ↓ Post-transplant hematopoiesis 12  
Vancomycin, 0.5 g/L
Neomycin, 1 g/L 
MHC-mismatched
BALB/c T cells → NK-depleted RAG1–/– B6 
Fed water ad libitum from d –7 to d 28 of transplant ↓ Microbial diversity
↓ Firmicutes
↑ Verrucomicrobia
↑ Proteobacteria
↓ Bacteroidetes 
↓ BM and spleen conventional T cells 13  
Imipenem/cilastatin, 100 mg/kg MHC-matched minor antigen–mismatched
B6 → 129S1 
Subcutaneous injected daily from d 10 to d 24 of transplant ↓ Clostridia,
↑ Verrucomicrobiales,
Akkermansia  
↓ Survival,
↑ GI GVHD,
↑ Donor CD4+ T cells, IL-23, and colonic granulocyte number  
17  
Imipenem/cilastatin, 50 mg/kg MHC-mismatched
B6 → BALB/c 
Gavaged daily from d –3 to d –1 of transplant ↑ Bacteroidaceae and Bacteroidales_S24-7_group,
↓ Porphyromonadaceae  
↓ Survival
↑ GVHD  
19  
Ampicillin, 1 g/L MHC-mismatched
B10.BR → B6 
Fed water ad libitum from d –21 to d –14 of transplant Lactobacillus
Blautia 
↓ Survival
↑ GI GVHD 
20  
Meropenem, 0.625 g/L MHC-mismatched
B6 → B6D2F1 
Fed water ad libitum from d 3 to d 15 of transplant ↓ Bacterial density
↓ α-diversity
↓ Clostridia
Bacteroides, Enterococcus, Erysipelatoclostridium, Bifidobacterium, and Akkermansia 
↓ Survival
↑ GI GVHD 
21  
Gentamicin, 0.5 g/L MHC-matched minor antigen–mismatched
B10.D2/nSnSlc → BALB/cCrSlc 
Orally administered from d –14 to d 28 of transplant Not mentioned ↓ cGVHD 22  
Polymyxin B, 100 mg/kg MHC-mismatched
B6 → B6D2F1 
Gavaged daily from d –4 to d 28 of transplant E coli ↑ Survival
↓ GVHD
↓ Donor T-cell expansion in the small intestine 
23  
Azithromycin, 100 mg/kg MHC-mismatched
B6 → BALB/c 
Gavaged daily from d –2 to d 2 of transplant Not mentioned ↑ Survival
↓ GVHD 
24  

↑ represents increase; ↓, decrease; and →, transplant to.

BM, bone marrow; cGVHD, chronic GVHD; IL-23, interleukin-23; NK, natural killer; Ref, reference.

Compared with aztreonam-treated mice.

Compared with imipenem/cilastatin- and galactooligosaccharide-treated mice.

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