Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, BW, Germany.
Transplantation. 2022 Nov 1;106(11):2155-2165. doi: 10.1097/TP.0000000000004161. Epub 2022 Oct 21.
The gut microbiota affects immune responses that cause organ transplant rejection, but the mechanisms by which this occurs remain poorly understood.
We have examined, in a murine model, how disruption of the gut microbiota with antibiotics early in life alters this microbial community later in life to affect immune responses that injure vascular allografts.
Analysis of 16S rRNA and whole genome sequencing of the gut microbiota demonstrated that early life disruption of this microbial community with antibiotics caused a reduction in taxa and enzymatic genes involved in the synthesis of acetate, an immunoregulatory metabolite in mice and humans. When allograft vascular injury was examined, early life disruption of the gut microbiota increased neutrophil accumulation and related medial injury of transplanted arteries. Normalizing the gut microbiota by co-housing and oral administration of acetate prevented neutrophil-mediated vascular allograft injury.
Dysbiosis of the gut microbiome that reduces its production of the immunoregulatory metabolite acetate exacerbates neutrophil-mediated allograft vascular injury.
肠道微生物群影响导致器官移植排斥的免疫反应，但这一过程的机制仍知之甚少。
我们在小鼠模型中研究了生命早期使用抗生素破坏肠道微生物群如何改变这种微生物群落，从而影响损害血管移植物的免疫反应。
对肠道微生物群的 16S rRNA 和全基因组测序分析表明，抗生素早期破坏这种微生物群落会导致参与合成乙酸的分类群和酶基因减少，乙酸是小鼠和人类的一种免疫调节代谢物。当检查血管同种异体移植物损伤时，肠道微生物群的早期破坏会增加中性粒细胞的积累，并导致移植动脉的中层损伤。通过共同饲养和口服乙酸使肠道微生物群正常化可预防中性粒细胞介导的血管同种异体移植物损伤。
肠道微生物组的生态失调会减少其免疫调节代谢物乙酸的产生，从而加剧中性粒细胞介导的移植物血管损伤。
