Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Aier Eye school of Ophthalmology, Central South University, Changsha 410083, China.
Int J Mol Sci. 2021 Apr 3;22(7):3745. 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.
慢性移植物抗宿主病（cGVHD）是异基因造血干细胞移植后最常见的并发症之一。据报道，肠道菌群失调和严重的微生物组损伤也与 GVHD 密切相关。在此，我们旨在阐明在 cGVHD 小鼠模型中给予各种抗生素的积极和消极影响。对于异基因骨髓移植（allo-BMT），将 B10.D2 小鼠的骨髓移植到 BALB/c 小鼠中以诱导 cGVHD。cGVHD 小鼠经口给予氨苄青霉素、庆大霉素（GM）、弗来霉素、万古霉素或溶剂载体（对照组）。在接受抗生素治疗的小鼠中，与对照组相比，GM 治疗组的全身性 cGVHD 表型和眼部 cGVHD 表现明显受到抑制。GM 治疗组的 cGVHD 靶向器官中的炎症细胞浸润和纤维化明显减轻。尽管 GM 治疗组中调节性 T 细胞保留水平较高，但这些小鼠的 cGVHD 靶向器官中的 Th17 细胞和产生白细胞介素（IL）-6 的巨噬细胞明显减少。总的来说，我们的结果表明，口服 GM 可能在 cGVHD 小鼠模型中发挥积极作用。
