Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, 08035 Barcelona, Spain.
Genome Res. 2010 Oct;20(10):1411-9. doi: 10.1101/gr.107987.110. Epub 2010 Aug 24.
The intestinal microbiota consists of over 1000 species, which play key roles in gut physiology and homeostasis. Imbalances in the composition of this bacterial community can lead to transient intestinal dysfunctions and chronic disease states. Understanding how to manipulate this ecosystem is thus essential for treating many disorders. In this study, we took advantage of recently developed tools for deep sequencing and phylogenetic clustering to examine the long-term effects of exogenous microbiota transplantation combined with and without an antibiotic pretreatment. In our rat model, deep sequencing revealed an intestinal bacterial diversity exceeding that of the human gut by a factor of two to three. The transplantation produced a marked increase in the microbial diversity of the recipients, which stemmed from both capture of new phylotypes and increase in abundance of others. However, when transplantation was performed after antibiotic intake, the resulting state simply combined the reshaping effects of the individual treatments (including the reduced diversity from antibiotic treatment alone). Therefore, lowering the recipient bacterial load by antibiotic intake prior to transplantation did not increase establishment of the donor phylotypes, although some dominant lineages still transferred successfully. Remarkably, all of these effects were observed after 1 mo of treatment and persisted after 3 mo. Overall, our results indicate that the indigenous gut microbial composition is more plastic that previously anticipated. However, since antibiotic pretreatment counterintuitively interferes with the establishment of an exogenous community, such plasticity is likely conditioned more by the altered microbiome gut homeostasis caused by antibiotics than by the primary bacterial loss.
肠道微生物群由超过 1000 种物种组成,它们在肠道生理学和动态平衡中发挥关键作用。这种细菌群落组成的失衡会导致肠道短暂功能障碍和慢性疾病状态。因此,了解如何操纵这个生态系统对于治疗许多疾病至关重要。在这项研究中,我们利用最近开发的深度测序和系统发育聚类工具,研究了外源性微生物群移植结合或不结合抗生素预处理的长期影响。在我们的大鼠模型中,深度测序揭示了肠道细菌多样性超过人类肠道的两倍到三倍。移植使受者的微生物多样性显著增加,这源于新的分类群的捕获和其他分类群丰度的增加。然而,当在抗生素摄入后进行移植时,所产生的状态只是个体治疗的重塑效果的组合(包括抗生素单独治疗引起的多样性降低)。因此,在移植前通过抗生素摄入降低受者细菌负荷并没有增加供体分类群的建立,尽管一些优势菌群仍然成功转移。值得注意的是,所有这些影响在 1 个月的治疗后观察到,并在 3 个月后持续存在。总体而言,我们的结果表明,土著肠道微生物组成比预期的更具可塑性。然而,由于抗生素预处理反直觉地干扰了外生群落的建立,这种可塑性可能更多地受到抗生素引起的肠道微生物组平衡改变的影响,而不是由主要细菌丧失引起的。