Antibiotic administration exacerbates acute graft vs. host disease-induced bone marrow and spleen damage in lymphopenic mice.
Antibiotic administration exacerbates acute graft vs. host disease-induced bone marrow and spleen damage in lymphopenic mice.
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DOI：
10.1371/journal.pone.0254845
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Grisham MB
中科院分区：
文献类型：
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作者：
McDaniel Mims B;Enriquez J;Pires Dos Santos A;Jones-Hall Y;Dowd S;Furr KL;Grisham MB
造血干细胞移植是治疗某些危及生命的恶性和非恶性疾病的潜在方法。然而，实验和临床研究表明，移植前的清髓调节会损害肠道，导致肠道细菌的易位和急性移植物抗宿主病（aGVHD）的发展。本研究的总体目的是确定广谱抗生素（Abx）的施用是否影响淋巴细胞减少小鼠的aGVHD的发病和/或严重程度，这些小鼠没有受到毒性，移植前调节。我们发现NK细胞缺失重组激活基因1缺陷（-NK/RAG）受体在过继移植同种异体CD4+ T细胞前7天和后4周接受含有万古霉素和新霉素的Abx鸡尾酒治疗，与未接受同种异体或同种异体T细胞移植的NK/RAG受体相比，agvhd诱导的BM衰竭和脾脏损伤加重。经abx治疗的小鼠表现出严重的贫血和单核细胞减少症，BM和脾脏免疫细胞明显减少。盲法组织病理学分析证实，移植同种异体T细胞的abx处理小鼠比未移植同种异体T细胞的小鼠对BM和脾脏的损伤明显更大。abx诱导的BM和脾脏损伤加重与粪便细菌多样性急剧减少、厌氧菌明显减少和潜在致病菌显著扩增相关。我们得出结论，持续的Abx治疗可能会通过减少短链脂肪酸产生的厌氧菌（如梭状芽胞杆菌，Blautia）和/或通过促进病原体（如Akkermansia）和机会致病菌（克罗诺杆菌）的扩张而加重agvhd诱导的组织损伤。
Hematopoietic stem cell transplantation is a potential cure for certain life-threatening malignant and nonmalignant diseases. However, experimental and clinical studies have demonstrated that pre-transplant myeloablative conditioning damages the gut leading to translocation of intestinal bacteria and the development of acute graft vs. host disease (aGVHD). The overall objective of this study was to determine whether administration of broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD in lymphopenic mice that were not subjected to toxic, pre-transplant conditioning. We found that treatment of NK cell-depleted recombination activating gene-1-deficient (-NK/RAG) recipients with an Abx cocktail containing vancomycin and neomycin for 7 days prior to and 4 weeks following adoptive transfer of allogeneic CD4+ T cells, exacerbated the development of aGVHD-induced BM failure and spleen damage when compared to untreated–NK/RAG recipients engrafted with syngeneic or allogeneic T cells. Abx-treated mice exhibited severe anemia and monocytopenia as well as marked reductions in BM- and spleen-residing immune cells. Blinded histopathological analysis confirmed that Abx-treated mice engrafted with allogeneic T cells suffered significantly more damage to the BM and spleen than did untreated mice engrafted with allogeneic T cells. Abx-induced exacerbation of BM and spleen damage correlated with a dramatic reduction in fecal bacterial diversity, marked loss of anaerobic bacteria and remarkable expansion of potentially pathogenic bacteria. We conclude that continuous Abx treatment may aggravate aGVHD-induced tissue damage by reducing short chain fatty acid-producing anaerobes (e.g. Clostridium, Blautia) and/or by promoting the expansion of pathobionts (e.g. Akkermansia) and opportunistic pathogens (Cronobacter).
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影响因子：
30.5
作者：
Mathewson ND;Jenq R;Mathew AV;Koenigsknecht M;Hanash A;Toubai T;Oravecz-Wilson K;Wu SR;Sun Y;Rossi C;Fujiwara H;Byun J;Shono Y;Lindemans C;Calafiore M;Schmidt TM;Honda K;Young VB;Pennathur S;van den Brink M;Reddy P
通讯作者：
Reddy P
影响因子：
64.8
作者：
Chassaing B;Koren O;Goodrich JK;Poole AC;Srinivasan S;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT
影响因子：
3.3
作者：
Moradigaravand, Danesh;Martin, Veronique;Parkhill, Julian
通讯作者：
Parkhill, Julian
影响因子：
4.4
作者：
Kaplan, DH;Anderson, BE;Shlomchik, WD
通讯作者：
Shlomchik, WD
DOI：
10.1038/nri3212
发表时间：
2012-05-11
期刊：
Nature reviews. Immunology
影响因子：
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作者：
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