Assessing microbiome population dynamics using wild-type isogenic standardized hybrid (WISH)-tags

<p><span>Microbiomes feature recurrent compositional structures under given environmental conditions. </span><span>However, these patterns may conceal diverse underlying population dynamics that require intra-strain resolution. Here, we developed a genomic tagging system, termed wild-type isogenic standardized hybrid (WISH)-tags, that can be combined with quantitative PCR and next-generation sequencing for microbial strain enumeration. We experimentally validated the performance of 62 tags and showed they can be differentiated with high precision. WISH-tags were introduced into model and non-model bacterial members of the mouse and plant microbiota. Intra-strain priority effects were tested using one species of isogenic barcoded bacteria in the murine gut and the <em>Arabidopsis</em> phyllosphere, both with and without microbiota context. We observed colonization resistance against late arriving strains of <em>Salmonella</em> typhimurium in the mouse gut, whereas the phyllosphere accommodated <em>Sphingomonas</em> latecomers in a proportional manner to their presence at the late inoculation timepoint. This demonstrates that WISH-tags are a resource for deciphering population dynamics underlying microbiome assembly across biological systems. </span></p>