Human gut microbiota development has been associated with healthy growth but understanding the determinants of community assembly and composition is a formidable challenge. We cultured bacteria from serially collected fecal samples from a healthy infant; 34 sequenced strains containing 103,102 genes were divided into two consortia representing earlier and later stages in community assembly during the first six postnatal months. The two consortia were introduced alone (singly), or sequentially in different order, or simultaneously into young germ-free mice fed human infant formula. The pattern of fitness of bacterial strains observed across the different colonization conditions indicated that later-phase strains substantially outcompete earlier-phase strains, although four early-phase members persist. Persistence was not determined by order of introduction, suggesting that priority effects are not prominent in this model. To characterize succession in the context of the metabolic potential of consortium members, we performed in silico reconstructions of metabolic pathways involved in carbohydrate utilization and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially collected fecal samples and their transcriptional responses to different histories of colonization. Applying feature-reduction methods disclosed a set of metabolic pathways whose presence and/or expression correlates with strain fitness and that enable early-stage colonizers to survive during introduction of later colonizers. The approach described can be used to test the magnitude of the contribution of identified metabolic pathways to fitness in different community contexts, study various ecological processes thought to govern community assembly, and facilitate development of microbiota-directed therapeutics.

中文翻译：

---

确定人类肠道微生物演替模型中细菌适应性的决定因素。


人类肠道微生物群的发育与健康生长相关，但了解群落组装和组成的决定因素是一项艰巨的挑战。我们从健康婴儿连续收集的粪便样本中培养细菌；包含 103,102 个基因的 34 个已测序菌株被分为两个群体，分别代表出生后前 6 个月内群落组装的早期和晚期阶段。将这两个联合体单独引入，或以不同的顺序相继引入，或同时引入喂养人类婴儿配方奶粉的年轻无菌小鼠中。在不同定植条件下观察到的细菌菌株的适应性模式表明，尽管有四个早期阶段成员仍然存在，但后期菌株在竞争中明显胜过早期菌株。持久性并不是由引入顺序决定的，这表明优先效应在该模型中并不突出。为了描述联盟成员代谢潜力背景下的演替特征，我们对涉及碳水化合物利用以及氨基酸和 B 族维生素生物合成的代谢途径进行了计算机重建，然后量化了连续收集的粪便样本中菌株的适合度（丰度）和他们对不同殖民历史的转录反应。应用特征减少方法揭示了一组代谢途径，其存在和/或表达与菌株适应性相关，并且使得早期殖民者能够在后期殖民者的引入期间存活。 所描述的方法可用于测试已确定的代谢途径对不同群落环境中健康的贡献程度，研究被认为控制群落组装的各种生态过程，并促进微生物群导向疗法的开发。