Gut microbiome connectivity drives mass host colonization and buffers against antibiotic-induced collapse

Abstract

Microbial dispersal continually shapes gut microbiomes, seeding communities during assembly and replenishing them after perturbation. Dispersals effect depends on its strength: low dispersal introduces stochasticity and drives divergence, whereas high dispersal increases mixing and promotes convergence. Although this pattern manifests across host-microbe systems, the mechanism by which dispersal alters colonization dynamics to generate such contrasting outcomes remains unclear. Identifying factors that toggle these dualistic effects is essential for predicting and controlling gut microbiome assembly and stability. We addressed this problem in gnotobiotic larval zebrafish, which is a tractable vertebrate model that enables experimental control and quantification of gut bacterial dispersal. To dissect the roles of dispersal, we defined the relationship between inoculation dose and colonization frequency for a model Vibrio cholerae isolate under different dispersal regimes. Strikingly, a dose yielding only 50% colonization in isolated hosts--the CD50--produced nearly universal colonization during co-housing, despite identical host and bacterial densities. Measurements of intestinal growth, carrying capacity, shedding, and environmental persistence were used to construct a quantitative colonization-dispersal model that explained the basis for this shift in colonization outcomes. At the CD50, colonization is inherently probabilistic, but once the first hosts become colonized, they reseed the environment and amplify secondary exposures, creating a feedback loop that rapidly transforms individual-level stochasticity into widespread colonization. We further show that this feedback operates in complex microbiomes, where larger host groups--with more opportunities for recolonization--buffer communities against antibiotic-induced collapse. Together, our findings demonstrate that dispersal regimes are not fixed but dynamically shift as hosts become increasingly connected. By revealing how dispersal and interhost transmission drive mass colonization and stabilize gut communities, our work identifies microbiome connectivity as a central mechanism governing gut microbial assembly and resilience.