Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Department of Infectious Diseases, The Six Affiliated Hospital, South China University of Technology, Foshan 528200, China.
Nutrients. 2022 Jul 6;14(14):2788. doi: 10.3390/nu14142788.
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.
肥胖和营养不良都会导致肠道菌群失调，并抑制视黄酸（RA）信号通路，而后者在生物过程中起着关键作用。本研究评估了一个假设，即结肠炎相关的肠道菌群失调也会对 RA 信号通路产生全身性的负面影响。因此，我们使用葡聚糖硫酸钠诱导的小鼠结肠炎模型研究了炎症（在维生素 A 充足的情况下）对 RA 信号通路的影响。数据表明，肠道炎症导致肝脏、大脑、肠道和脂肪组织中 RA 信号转导减少，通过分析编码 RA 合成、氧化、运输和受体的基因的表达来衡量。结肠炎小鼠中 RA 调节的肠道归巢分子（包括 α4β7 整合素和 CCR9）的表达减少，同时 MADCAM1 的表达减少，这表明由于 RA 信号转导减少，免疫功能受损。数据还表明，结肠炎的发展伴随着肠道菌群失调，其特征是乳杆菌科和疣微菌科减少，而肠杆菌科和其他科增加。结肠炎导致产丁酸细菌减少和产甲烷细菌增加。此外，肠道菌群失调与结肠中诱导的 Il-1β、Ifn-γ 和 Tnf-α mRNA 增加，但 Il-22、Il-17f 和 Rorγt 转录物减少有关。总之，肠道炎症会抑制多个器官中的 RA 信号转导。RA 在调节各种生物过程中是必不可少的，即使不存在维生素 A 缺乏，检测组织中 RA 信号转导的减少也是至关重要的。此外，益生菌可能有助于预防肠道菌群失调和逆转受损的 RA 信号转导，从而带来全身性的健康益处。
