Castro-Mejía Josué L, Jakesevic Maja, Fabricius Niels F, Krych Łukasz, Nielsen Dennis S, Kot Witold, Bendtsen Katja M, Vogensen Finn K, Hansen Camilla H F, Hansen Axel K
Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg, Denmark.
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1870 Frederiksberg, Denmark.
Res Vet Sci. 2018 Jun;118:357-364. doi: 10.1016/j.rvsc.2018.03.013. Epub 2018 Mar 27.
Ampicillin is applied in rodents to induce a temporarily depleted microbiota. To elucidate whether bacteria are just temporarily suppressed or fully eliminated, and how this affects the re-colonisation process, we compared the microbiota and immune system in conventionally housed untreated mice with newly weaned ampicillin treated mice subsequently housed in either a microbe containing environment or in an isolator with only host associated suppressed bacteria to recolonize the gut. Two weeks ampicillin treatment induced a seemingly germ-free state with no bacterial DNA to reveal. Four weeks after treatment caeca were still significantly enlarged in both treated groups, but bacteria re-appeared even in isolator housed mice. While some suppressed bacteria were able to recover and even dominate the community, the abundances and composition were far from the untreated mice and differed between isolator and conventional housing. The treatment reduced the innate cytokine expressions at least for three weeks after treatment, and had a non-lasting reducing impact on the regulatory T cells, and a more lasting impact on the natural killer T cells. We conclude that temporary ampicillin treatment suppresses the majority but does not eliminate all the gut microbiota members. The re-colonisation process is as such influenced by both suppressed host associated bacteria and by environmental bacteria. Treated mice do not re-obtain a complex gut microbiota comparable to untreated mice, and the immune response and gut morphology reflect this. This is a concern when comparing host parameters sensitive to microbial regulation after an antibiotic-induced temporarily "germ-free" state.
氨苄青霉素被应用于啮齿动物以诱导暂时的微生物群耗竭。为了阐明细菌是仅仅被暂时抑制还是被完全消除，以及这如何影响重新定殖过程，我们比较了常规饲养的未处理小鼠与新断奶后用氨苄青霉素处理的小鼠的微生物群和免疫系统，后者随后被饲养在含有微生物的环境中或仅含有与宿主相关的受抑制细菌的隔离器中以使肠道重新定殖。两周的氨苄青霉素治疗诱导出一种看似无菌的状态，没有细菌DNA可检测到。治疗四周后，两个治疗组的盲肠仍明显肿大，但即使在隔离器饲养的小鼠中也重新出现了细菌。虽然一些受抑制的细菌能够恢复甚至在群落中占主导地位，但丰度和组成与未处理的小鼠相差甚远，并且在隔离器和常规饲养环境之间也有所不同。治疗至少在治疗后三周降低了先天细胞因子的表达，对调节性T细胞有非持久性的降低影响，对自然杀伤T细胞有更持久的影响。我们得出结论，临时的氨苄青霉素治疗抑制了大多数但并未消除所有肠道微生物群成员。重新定殖过程因此受到受抑制的与宿主相关的细菌和环境细菌的影响。经治疗的小鼠无法重新获得与未处理小鼠相当的复杂肠道微生物群，免疫反应和肠道形态也反映了这一点。在比较抗生素诱导的暂时“无菌”状态后对微生物调节敏感的宿主参数时，这是一个需要关注的问题。
