Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease

• Published in: International journal of molecular sciences Vol. 22; no. 7; p. 3745
• Main Authors: Sato, Shinri, Shimizu, Eisuke, He, Jingliang, Ogawa, Mamoru, Asai, Kazuki, Yazu, Hiroyuki, Rusch, Robert, Yamane, Mio, Yang, Fan, Fukuda, Shinji, Kawakami, Yutaka, Tsubota, Kazuo, Ogawa, Yoko
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2021; MDPI
• Subjects: Administration, Oral; Allografts; Ampicillin; Analysis; Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bone marrow; Bone Marrow Transplantation; Chronic Disease; Colon; Cornea; dry eye disease; Dysbacteriosis; Eye diseases; Female; Fibrosis; Genotype & phenotype; Gentamicin; Graft vs Host Disease - drug therapy; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Graft-versus-host reaction; graft-vs-host disease; Helper cells; Hematopoietic stem cells; Immunoregulation; Inflammation; Interleukin-6 - immunology; Interleukins; Liver; Lungs; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Macrophages - pathology; Metronidazole; Mice; Mice, Inbred BALB C; microbiome; Microbiomes; Microbiota; Mortality; Oral administration; Organs; Phenotypes; Rodents; Stem cell transplantation; Stem cells; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Th17 Cells - immunology; Th17 Cells - pathology; Transplantation; Vancomycin; Japan; gentamicin; dry eye disease; graft-vs-host disease; antibiotics; microbiome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22073745

Chronic graft-versus-host disease (cGVHD) is one of the most frequent complications experienced after allogeneic hematopoietic stem cell transplantation. Reportedly, dysbiosis and severe damage to the microbiome are also closely associated with GVHD. Herein, we aimed to elucidate the positive and negative effects of the administration of various antibiotics in a murine model of cGVHD. For allogeneic bone marrow transplantation (allo-BMT), bone marrow from B10.D2 mice were transplanted in BALB/c mice to induce cGVHD. The cGVHD mice were orally administered ampicillin, gentamicin (GM), fradiomycin, vancomycin, or the solvent vehicle (control group). Among the antibiotic-treated mice, the systemic cGVHD phenotypes and ocular cGVHD manifestations were suppressed significantly in GM-treated mice compared to that in control mice. Inflammatory cell infiltration and fibrosis in cGVHD-targeted organs were significantly attenuated in GM-treated mice. Although regulatory T cells were retained at greater levels in GM-treated mice, there were significantly fewer Th17 cells and interleukin (IL)-6-producing macrophages in cGVHD-targeted organs in these mice. Collectively, our results revealed that orally administered GM may exert positive effects in a cGVHD mouse model.