Talavera-Marcos, S.; Aguirre de Carcer, D.

We describe a top-down engineering approach that leverages ecological drift to generate Minimal Microbiomes; microbial consortia that are relatively simple, cohesive, and functionally complete. This process can be applied to any microbial ecosystem, provided that the target microbiome can be experimentally mimicked. Empirical support for this approach has emerged from multiple independent studies. Here, we use simulations across diverse scenarios, significantly varying niche structures and biotic interactions, to explore the experimental conditions and source microbiome characteristics that favor successful outcomes. Our results indicate that the effectiveness of this approach is constrained by several factors, and that perfect outcomes should not be routinely expected. Nevertheless, despite its drawbacks, this strategy remains a powerful tool for simplifying microbiomes and isolating key co-adapted populations, enabling the construction of low-diversity consortia that retain community function and present ecological cohesion.