Commensal priming of zebrafish embryos impacts their offspring mucosal immunity and disease resistance

The rearing medium tonicity and the commensal microorganisms that reside in mucosal surfaces in vertebrates have emerged as a critical source of environmentally-derived stimuli that can impact health and disease. Despite the underlying cellular and molecular mechanisms related to these changes are just beginning to be defined, the long-term effects and the possible heritability of these early microbes-host interactions have not been well studied. This study sought to investigate whether a lack of bacterial priming in newly hatched embryos affects development, survival, life span, and immune competence. To address this hypothesis, we raised wild-type zebrafish (ZF) in either germ-free (GF) or conventional (CONR) conditions until 7 days post fertilization (dpf). After that, GF and CONR larvae were housed in our general ZF facility and reared indefinitely in similar diets and environmental conditions. Starting from 10 dpf, growth, survival, and histological changes in the gut were analyzed and recorded for several months. Surprisingly, morphometric measurements revealed that ex-GF animals present a greater size and show reduced natural mortality than their CONR siblings. Moreover, gut morphology observations through histochemical preparations of 90 dpf ZF revealed a significantly reduced number of goblet cells, suggesting a reduced mucus hydrogel layer in ex-GF ZF. Strikingly, the offspring of ex-GF animals were more susceptible to a bacterial challenge. Studies are in progress to reveal the mechanisms involved in commensal priming at the early developmental stages in immunity, including the analysis of gene expression profiles and the epigenetic changes taking place on such genes.