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

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

doi:10.3390/ijms22073745

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

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Yoko Ogawa

Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan

Aier Eye school of Ophthalmology, Central South University, Changsha 410083, China

Department of Ophthalmology, Tsurumi University School of Dental Medicine, Kanagawa 230-0063, Japan

⁴

Institute for Advanced Biosciences, Keio University, Yamagata 997-0052, Japan

⁵

Transborder Medical Research Center, University of Tsukuba, Ibaraki 305-8575, Japan

⁶

Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kanagawa 210-0821, Japan

⁷

Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan

⁸

International University of Health and Welfare School of Medicine, Chiba 286-0048, Japan

Authors to whom correspondence should be addressed.

Academic Editor: Philipp Steven

Int. J. Mol. Sci. 2021, 22(7), 3745; https://doi.org/10.3390/ijms22073745

Received: 26 February 2021 / Revised: 26 March 2021 / Accepted: 31 March 2021 / Published: 3 April 2021

(This article belongs to the Special Issue Pathophysiological Mechanisms in Ocular Graft-versus-Host Disease)

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Abstract

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. View Full-Text

Keywords: graft-vs-host disease; antibiotics; microbiome; dry eye disease; gentamicin

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Sato, S.; Shimizu, E.; He, J.; Ogawa, M.; Asai, K.; Yazu, H.; Rusch, R.; Yamane, M.; Yang, F.; Fukuda, S.; Kawakami, Y.; Tsubota, K.; Ogawa, Y. Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease. Int. J. Mol. Sci. 2021, 22, 3745. https://doi.org/10.3390/ijms22073745

AMA Style

Sato S, Shimizu E, He J, Ogawa M, Asai K, Yazu H, Rusch R, Yamane M, Yang F, Fukuda S, Kawakami Y, Tsubota K, Ogawa Y. Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease. International Journal of Molecular Sciences. 2021; 22(7):3745. https://doi.org/10.3390/ijms22073745

Chicago/Turabian Style

Sato, Shinri, Eisuke Shimizu, Jingliang He, Mamoru Ogawa, Kazuki Asai, Hiroyuki Yazu, Robert Rusch, Mio Yamane, Fan Yang, Shinji Fukuda, Yutaka Kawakami, Kazuo Tsubota, and Yoko Ogawa. 2021. "Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease" International Journal of Molecular Sciences 22, no. 7: 3745. https://doi.org/10.3390/ijms22073745

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

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