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

Reegan J Willms,Lena O Jones,Edan Foley,Jennifer C Hocking

doi:10.1016/j.celrep.2022.110311

Abstract

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.

Highlights

Research conducted with a variety of model organisms has revealed much about the importance of gut microbes for host health
Zebrafish larvae have emerged as a valuable tool to identify key regulators of host-microbe interactions (Brugman, 2016; Flores et al, 2020; Lopez Nadal et al, 2020)
A single-cell atlas of the zebrafish larval intestine To trace effects of commensal microbes on intestinal physiology, we prepared single-cell transcriptional profiles of digestive tracts from 6 dpf zebrafish larvae raised under conventional (CV) or GF conditions (Figures 1A and S1)

Summary

Introduction

Research conducted with a variety of model organisms has revealed much about the importance of gut microbes for host health. It is critical to fully understand how the microbiota impact development, growth, and cellular function of host organisms. Once larvae exit the chorion, water-borne microbes colonize the gut lumen (Bates et al, 2006; Stephens et al, 2016; Wallace et al, 2005), where they influence host development (Bates et al, 2006; Cheesman et al, 2011; Kanther et al, 2011; Koch et al, 2018). Zebrafish provide a convenient window to visualize microbial controls of vertebrate physiology

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Discussion

Conclusion