Multi-kingdom ecological drivers of microbiota assembly in preterm infants

The preterm infant gut microbiota develops remarkably predictably(1–7), with pioneer species colonizing after birth, followed by an ordered succession of microbes. The gut microbiota is vital to preterm infant health(8,9) yet the forces underlying these predictable dynamics remain unknown. The environment, the host, and microbe-microbe interactions are all likely to shape microbiota dynamics, but in such a complex ecosystem identifying the specific role of any individual factor has remained a major challenge(10–14). Here we use multi-kingdom absolute abundance quantitation, ecological modelling, and experimental validation to overcome this challenge. We quantify the absolute bacterial, fungal, and archaeal dynamics in a longitudinal cohort of 178 preterm infants. We uncover, with exquisite precision, microbial blooms and extinctions and reveal an inverse correlation between bacterial and fungal loads in the infant gut. We infer computationally and demonstrate experimentally in vitro and in vivo that predictable assembly dynamics may be driven by directed, context-dependent interactions between specific microbes. Mirroring the dynamics of macroscopic ecosystems(15–17), a late-arriving member, Klebsiella, exploits the pioneer, Staphylococcus, to gain a foothold within the gut. Remarkably, we find that interactions between kingdoms can influence assembly, with a single fungal species, Candida albicans, inhibiting multiple dominant gut bacteria. Our work unveils the centrality of simple microbe-microbe interactions in shaping host-associated microbiota, critical for both our understanding of microbiota ecology and targeted microbiota interventions.