Impact of vitamin A transport and storage on intestinal retinoid homeostasis and functions.

Lecithin:retinol acyltransferase (LRAT) and retinol-binding protein (RBP) enable vitamin A storage and transport, respectively, maintaining tissue homeostasis of retinoids (vitamin A derivatives). The precarious vitamin A status of the Lrat-/-Rbp-/- mice rapidly deteriorates upon dietary vitamin A restriction, leading to signs of severe vitamin A deficiency (VAD). As retinoids impact gut morphology and functions, VAD is often linked to intestinal pathological conditions and microbial dysbiosis. Thus, we investigated the contribution of vitamin A storage and transport to intestinal retinoid homeostasis and functionalities. We showed the occurrence of intestinal VAD in Lrat-/-Rbp-/- mice, demonstrating the critical role of both pathways in preserving gut retinoid homeostasis. Moreover, in the mutant colon, VAD resulted in compromised intestinal barrier as manifested by reduced mucins and antimicrobial defense, leaky gut, increased inflammation and oxidative stress, and altered mucosal immunocytokine profiles. These perturbations were accompanied by fecal dysbiosis, revealing that the vitamin A status (sufficient vs. deficient), rather than the amount of dietary vitamin A per se, is likely a major initial discriminant of the intestinal microbiome. Our data also pointed to a specific fecal taxonomic profile and distinct microbial functionalities associated with VAD. Overall, our findings revealed the suitability of the Lrat-/-Rbp-/- mice as a model to study intestinal dysfunctions and dysbiosis promoted by changes in tissue retinoid homeostasis induced by the host vitamin A status and/or intake.