A cell atlas of microbe-responsive processes in the zebrafish intestine

Gut microbial products direct growth, differentiation, and development in animal hosts. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled cell transcriptomes from the intestine, and associated tissue, of zebrafish larvae raised in the presence or absence of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome that included regulatory effects on patterning and on metabolic and immune activity. For example, we showed that the absence of microbes hindered pro-angiogenic signals in the developing vasculature, causing impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type. [Display omitted] •Zebrafish possess genetically distinct IEC populations•Zebrafish have IECs analogous to mammalian progenitor, Best4/Otop2, and tuft cells•Microbes alter unique transcriptional pathways within intestinal cell subtypes•Microbes promote intestinal angiogenesis Willms et al. profile single cells from intestines of zebrafish raised in the presence or absence of bacteria to identify microbe-dependent processes at the cellular level. They uncover extensive cellular heterogeneity in the zebrafish gut and describe how microbial colonization alters gene expression within each cell type.