Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Transplantation. 2018 Jul;102(7):1085-1095. doi: 10.1097/TP.0000000000002169.
The gut microbiota influences many immunological processes but how its disruption affects transplant rejection is poorly understood.
Interposition grafting of aortic segments was used to examine vascular rejection. The gut microbiota was disrupted in graft recipients using an antibiotic cocktail (ampicillin, vancomycin, metronidazole, neomycin sulfate) in their drinking water.
Treatment of mice with antibiotics severely reduced total bacterial content in the intestine and disrupted the bacterial composition. Short-term treatment of mice for only the first 3 weeks of life resulted in the population of the intestine in mature mice with bacterial communities that were mildly different from untreated mice, containing slightly more Clostridia and less Bacteroides. Antibiotic disruption of the gut microbiota of graft recipients, either for their entire life or only during the first 3 weeks of life, resulted in increased medial injury of allograft arteries that is reflective of acute vascular rejection but did not affect intimal thickening reflective of transplant arteriosclerosis. Exacerbated vascular rejection resulting from disruption of the gut microbiota was related to increased infiltration of allograft arteries by neutrophils.
Disruption of the gut microbiota early in life results in exacerbation of immune responses that cause acute vascular rejection.
肠道微生物群影响许多免疫过程，但肠道微生物群的破坏如何影响移植排斥反应尚不清楚。
使用主动脉段间置移植来检查血管排斥。通过在饮用水中添加抗生素鸡尾酒（氨苄西林、万古霉素、甲硝唑、硫酸新霉素）来破坏移植物受者的肠道微生物群。
用抗生素处理的小鼠肠道内的总细菌含量严重减少，细菌组成也被破坏。仅在生命的前 3 周对小鼠进行短期治疗，导致成熟小鼠肠道中的细菌群落与未处理的小鼠略有不同，含有更多的梭菌和更少的拟杆菌。无论是在整个生命过程中还是仅在前 3 周的生命过程中，用抗生素破坏移植物受者的肠道微生物群，都会导致同种异体动脉的中层损伤增加，这反映了急性血管排斥反应，但不会影响反映移植动脉硬化的内膜增厚。肠道微生物群破坏导致的血管排斥反应加剧与移植物动脉中中性粒细胞的浸润增加有关。
生命早期肠道微生物群的破坏会导致引起急性血管排斥的免疫反应加剧。
