Exposure to retinoids for the treatment of acne has been linked to the etiology of inflammatory bowel disease (IBD). The intestinal
mucus layer is an important structural barrier that is disrupted in IBD. Retinoid-induced alteration of mucus physiology has
been postulated as a mechanism linking retinoid treatment to IBD; however, there is little direct evidence for this interaction.
The zebrafish larva is an emerging model system for investigating the pathogenesis of IBD. Importantly, this system allows
components of the innate immune system, including mucus physiology, to be studied in isolation from the adaptive immune system.
This study reports the characterization of a novel zebrafish larval model of IBD-like enterocolitis induced by exposure to
dextran sodium sulfate (DSS). The DSS-induced enterocolitis model was found to recapitulate several aspects of the zebrafish
trinitrobenzene-sulfonic-acid (TNBS)-induced enterocolitis model, including neutrophilic inflammation that was microbiota-dependent
and responsive to pharmacological intervention. Furthermore, the DSS-induced enterocolitis model was found to be a tractable
model of stress-induced mucus production and was subsequently used to identify a role for retinoic acid (RA) in suppressing
both physiological and pathological intestinal mucin production. Suppression of mucin production by RA increased the susceptibility
of zebrafish larvae to enterocolitis when challenged with enterocolitic agents. This study illustrates a direct effect of
retinoid administration on intestinal mucus physiology and, subsequently, on the progression of intestinal inflammation.