Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life.

人类微生物群组装从出生时开始，由母体和环境微生物播种。生态学理论假设初级定植者决定了微生物群落组装结果，但这种微生物在人类肠道中的优先影响仍未得到充分探索。在这里，使用纵向粪便宏基因组学，我们表征了来自英国的 1,288 名新生儿的新生儿微生物群组装。我们表明，开创性的新生儿肠道微生物群可以分为三种不同的群落状态之一，每种状态都由单一微生物物种主导，并受临床和宿主因素的影响，例如产妇年龄、种族和胎次。以粪肠球菌为主的群落状态表现出随机微生物群组装，并在婴儿期持续高病原体负荷。相比之下，以双歧杆菌为主的群落状态，特别是长双歧杆菌，特别是短双歧杆菌，表现出稳定的组装轨迹和长期的病原体定植抗性，这可能是由于菌株特异性功能适应富含母乳的新生儿饮食。与我们的人类队列观察一致，短双歧杆菌在无菌小鼠模型中表现出优先效应并赋予病原体定植抗性。我们的研究结果巩固了双歧杆菌作为初级定植者在塑造早期微生物群组装和功能方面的关键作用。