Lecithin:retinol acyltransferase and
retinol-binding protein enable
vitamin A (VA) storage and transport, respectively, maintaining tissue homeostasis of
retinoids (VA derivatives). The precarious VA status of the
lecithin:retinol acyltransferase-deficient (Lrat-/-)
retinol-binding protein-deficient (Rbp-/-) mice rapidly deteriorates upon dietary VA 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 VA 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 a 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 VA status (sufficient vs. deficient), rather than the amount of dietary VA 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 VA status and/or intake.