靶向肠道菌群已显示出预防实验性急性肾损伤（AKI）的前景，但是这方面未研究加速恢复和预防纤维化的作用。在这里，我们发现，在小鼠严重缺血性肾损伤后使用抗生素（尤其是阿莫西林）改变肠道菌群可以加速恢复。这些恢复指标包括肾小球滤过率、肾纤维化的减少以及肾脏前纤维化基因表达的降低。发现阿莫西林可以增加粪便中的Alistipes、Odoribacter和Stomatobaculum物种，同时显著减少Holdemanella和Anaeroplasma。具体来说，阿莫西林治疗减少了肾脏CD4+T细胞、白细胞介素（IL）-17+CD4+T细胞和肿瘤坏死因子-α双阴性T细胞，同时增加了CD8+T细胞和PD1+CD8+T细胞。阿莫西林还增加了肠道基质细胞CD4+T细胞，同时减少了CD8+T和IL-17+CD4+T细胞。阿莫西林在无菌或缺乏CD8+T淋巴细胞的小鼠中未加速修复，表明阿莫西林的保护作用依赖于微生物组和CD8+T淋巴细胞。不过，在缺乏CD4+T的小鼠中，阿莫西林仍有效。从阿莫西林治疗到无菌小鼠的粪便微生物移植减少了肾脏纤维化，增加了Foxp3+CD8+T细胞。在肾双侧缺血再灌注损伤中，阿莫西林预处理保护了小鼠，但在顺铂诱导的AKI中并未加速修复。因此，在严重缺血性AKI后使用阿莫西林修饰肠道细菌是一种有前途的新型治疗方法，可以加速肾功能恢复并减轻AKI进展为慢性肾脏疾病的过程。 版权所有 © 2023. Elsevier Inc. 发布。

Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included the glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4+T cells, interleukin (IL)-17 +CD4+T cells, and tumor necrosis factor-α double negative T cells while it increased CD8+T cells and PD1+CD8+T cells. Amoxicillin also increased gut lamina propria CD4+T cells while decreasing CD8+T and IL-17+CD4+T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8+T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3+CD8+T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.Copyright © 2023. Published by Elsevier Inc.