Preclinical evidence: role of antibiotics in modulating microbiota and outcomes of HCT
| Antibiotics . | Model . | Method . | Effects on microbiome . | Outcomes . | Ref . |
|---|---|---|---|---|---|
| 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 |
| Antibiotics . | Model . | Method . | Effects on microbiome . | Outcomes . | Ref . |
|---|---|---|---|---|---|
| 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 |