Chronic early life stress alters the microbial and transcriptional profile of the zebrafish gut

Chronic early life stress (ELS) is appreciated to potently shape a myriad of biological outcomes later in life and has been associated with fertility deficits and the onset of gastrointestinal dysfunction in humans. Further, recent longitudinal cohort studies demonstrate that multigenerational adversity impacts the gut microbiome composition in early childhood, highlighting the gut-brain axis as an important target of ELS. Building on our recently published work demonstrating that ELS alters the neuroimmune profile of the developing zebrafish gut, our goal here was to establish a model of multigenerational ELS in zebrafish and determine cumulative stress impacts on fertility, gut microbial composition and the transcriptional landscape of the developing gut. Wild-type zebrafish were exposed to chronic ELS beginning at 6 dpf until 30 dpf according to our recently published stress paradigm for a total of four successive generations. We compared stressed and unstressed groups from either stressed or unstressed lineages and found that chronic ELS was associated with reduced egg viability and profound changes to the gut microbiome. RNA-sequencing revealed ELS-associated differential expression of more than 800 genes in founder generations. Altogether our data demonstrate that zebrafish are a powerful model for exploring neuroimmune interactions at mucosal surfaces across generations.