Quickly after birth, the gut microbiota is shaped via species acquisition and resource pressure. Breastmilk, and more specifically, human milk oligosaccharides are a determining factor in the formation of microbial communities and the interactions between bacteria. Prominent human milk oligosaccharide degraders have been rigorously characterized, but it is not known how the gut microbiota is shaped as a complex community. Here, we designed BIG-Syc, a synthetic community of 13 strains from the gut of vaginally born, breastfed infants. BIG-Syc replicated key compositional, metabolic, and proteomic characteristics of the gut microbiota of infants. Upon fermentation of a 4 and 5 human milk oligosaccharide mix, BIG-Syc demonstrated different compositional and proteomic profiles, with Bifidobacterium infantis and Bifidobacterium bifidum suppressing one another. The mix of 5 human milk oligosaccharides resulted in a more diverse composition with dominance of B. bifidum, whereas that with 4 human milk oligosaccharides supported the dominance of B. infantis, in 4 of 6 replicates. Reintroduction of bifidobacteria to BIG-Syc led to their engraftment and establishment of their niche. Based on proteomics and genome-scale metabolic models, we reconstructed the carbon source utilization and metabolite and gas production per strain. BIG-Syc demonstrated teamwork as cross-feeders utilized simpler carbohydrates, organic acids, and gases released from human milk oligosaccharide degraders. Collectively, our results showed that human milk oligosaccharides prompt resource-sharing for their complete degradation while leading to a different compositional and functional profile in the community. At the same time, BIG-Syc proved to be an accurate model for the representation of intra-microbe interactions.

中文翻译：

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母乳低聚糖组合中婴儿肠道微生物群合成群落的资源共享


出生后不久，肠道微生物群是通过物种获取和资源压力形成的。母乳，更具体地说，母乳低聚糖是微生物群落形成和细菌之间相互作用的决定性因素。著名的母乳低聚糖降解物已被严格表征，但尚不清楚肠道微生物群是如何形成一个复杂的群落的。在这里，我们设计了 BIG-Syc，这是一个由来自阴道出生、母乳喂养婴儿肠道的 13 种菌株组成的合成群落。BIG-Syc 复制了婴儿肠道微生物群的关键组成、代谢和蛋白质组学特征。在 4 和 5 人乳低聚糖混合物发酵后，BIG-Syc 表现出不同的组成和蛋白质组学特征，婴儿双歧杆菌和两歧双歧杆菌相互抑制。5 种人乳低聚糖的混合物导致更多样化的组成，以两歧双歧杆菌为主，而含有 4 种人乳低聚糖的低聚糖支持婴儿双歧杆菌的优势，在 6 个重复中的 4 个。将双歧杆菌重新引入 BIG-Syc 导致它们植入并建立自己的生态位。基于蛋白质组学和基因组规模的代谢模型，我们重建了每个菌株的碳源利用率以及代谢物和气体产生量。BIG-Syc 展示了团队合作，因为交叉喂食者利用了更简单的碳水化合物、有机酸和母乳低聚糖降解剂释放的气体。总的来说，我们的结果表明，母乳低聚糖促进了资源共享以实现其完全降解，同时导致社区中的组成和功能特征不同。 同时，BIG-Syc 被证明是表示微生物内部相互作用的准确模型。