Interaction between dietary vitamin A, gut microbes, and host vitamin A status

Abstract

Micronutrient deficiency during childhood, impairs microbiome development and establishment, ultimately affecting nutrient absorption and promoting inflammatory responses, especially in the gut, in a sort of vicious cycle1. Vitamin A is an essential micronutrient that regulates many critical biological functions, such as vision, reproduction and immunity, and that more generally contributes to the integrity of the epithelia by modulating cellular proliferation and differentiation 2. Vitamin A‐deficiency (VAD) is an overwhelming and still intractable public health problem3. The essential nutrient vitamin A regulates intestinal functions by modulating inflammation, gut immunity, and intestinal cell proliferation. Thus, the vitamin A status has a profound impact on intestinal health and, indeed, VAD is often associated with pathological conditions of the gut. On the other hand, a healthy intestine is critical to support a “healthy” microbiome which in turn helps maintaining proper intestinal functions in a feedback loop.To gain further understanding of the complex interplay between vitamin A, host physiology and microbiome, we used Lrat−/−Rbp−/−mice as a model of marginal VAD 4, when maintained on a vitamin A‐sufficient diet, and of severe VAD when deprived of dietary vitamin A. Due to the absence of lecithin:retinol acyltransferase (LRAT) and retinol‐binding protein (RBP), these mice cannot store and mobilize, respectively, hepatic vitamin A towards the periphery of the body. Thus, they rely exclusively on dietary vitamin A to support vitamin A‐dependent functions4. At 6 weeks of age, Lrat−/−Rbp−/− and WT mice were placed on either vitamin A‐sufficient or ‐deficient diet for 4 weeks and then returned to the initial regular chow regimen for 1 week. Various tissues, including intestine, and feces were collected at different time points throughout the experiment. We confirmed that VAD impairs intestinal vitamin A homeostasis and barrier functions (reduced antimicrobial defense and mucus production; increased oxidative stress; leaky gut). Genomic sequencing of the fecal 16S RNA showed that fecal dysbiosis is concomitant with the VAD status rather than the dietary vitamin A content per se, even though the degree of deficiency (marginal vs severe) did not further affect the dysbiosis. Instead, a preliminary analysis of microbial functionalities showed a significant separation of the microbial populations between vitamin A sufficient, marginal VAD and severe VAD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.