Retinoic Acid Signaling Is Compromised in DSS-Induced Dysbiosis

Abstract

Obesity and malnutrition both cause dysbiosis and dampen retinoic acid (RA) signaling pathways, which play pivotal roles in biological processes. The current study evaluates a hypothesis that colitis-associated dysbiosis also has systemic negative impacts on RA signaling. Thus, we studied the effects of inflammation, under a vitamin A-sufficient condition, on RA signaling using mouse colitis models induced by dextran sulfate sodium. That data showed that intestinal inflammation resulted in reduced RA signaling in the liver, brain, gut, and adipose tissues measured by analyzing the expression of genes encoding for the synthesis, oxidation, transport, and receptor of RA. The expression of RA-regulated gut homing molecules including α4β7 integrin, and CCR9, along with MADCAM1 were all reduced in colitis mice revealing compromised immunity due to reduced RA signaling. The data also showed that the development of colitis was accompanied by dysbiosis featured with reduced Lactobacillaceae and Verrucomicrobiaceae but an expansion of Erysipelotrichaceae and others. Colitis resulted in reduced butyrate-producing bacteria and increased methane-generating bacteria. Additionally, dysbiosis was associated with induced Il-1β, Ifn-γ, and Tnf-α mRNA but reduced Il-22, Il-17f, and Rorγt transcripts in the colon. Together, intestinal inflammation inhibits RA signaling in multiple organs. RA is essential in regulating various biological processes, it is critical to detect RA signaling reduction in tissues even when vitamin A deficiency is absent. Moreover, probiotics can potentially prevent dysbiosis and reverse compromised RA signaling, having systemic health benefits.