Responses to invasion and antibiotics by model gut microbiomes in zebrafish

The responses of the gut microbiome to perturbations such as invading species or antibiotic drugs remain poorly understood. Can community response be predicted from the response of individual species? Does the physical structure of the gut and its constituents influence outcomes of perturbations? We explore these questions using larval zebrafish, an organism that combines physiological relevance, biological control, and optical accessibility. Performing gut dissection to quantify species abundance and light sheet fluorescence microscopy to visualize 3D structure and morphology in live animals, we assess the impact of two types of perturbations on gut communities composed of one to three bacterial species. The first involves sub-lethal doses of the antibiotic ciprofloxacin, for which we find striking differences between in vitro and in vivo responses, in some cases with inversion of competitive advantages among species pairs. Imaging shows changes in bacterial morphology and behavior that influence the ability to persist in the gut. The second perturbation involves invasion by a new bacterial species armed with a toxin injection apparatus, upon which all initially colonizing species and combinations of species are reduced in abundance, but by differing magnitudes. These observations help reveal factors such as species diversity that determine gut microbiome composition and stability.