Effects of High-Dose Genistein on the Hypothalamic RNA Profile and Intestinal Health of Female Chicks

Genistein is abundant in animal feed. In this study,
the side effects of high-dose genistein on intestinal health and hypothalamic
RNA profile were evaluated. Chicks exposed to high-dose genistein
by intraperitoneal injection (416 ± 21, 34.5 ± 2.5) and
feed supplementation (308 ± 19, 27.2 ± 2.1) both showed
a reduced body weight gain and feed intake in comparison with the
control group (261 ± 16, 22.7 ± 1.6, P <
0.01). In comparison with the control (22.4 ± 0.5, 33.3 ±
2.4), serum levels of albumin and total protein were decreased after
high-dose genistein injection (21.6 ± 0.5, 31.8 ± 1.6) and
diet supplementation (20.6 ± 0.9, 29.9 ± 2.5, P < 0.001). Interestingly, the genistein diet presented the chick
hypothalamus with downregulated expression of bitter receptors (TAS1R3, P < 0.05). Meanwhile, it upregulated the expressions
of TAS2R1 (P < 0.05) and downstream genes (PLCB2
and IP3R3) in the ileum (P < 0.05). Accordingly,
high-dose dietary genistein reduced villus height and the abundance
of Lactobacillus, along with the increased
abundance of pathogenic bacteria in the ileum (P <
0.05). Furthermore, transcriptomic analysis identified 348 differently
expressed genes (168 upregulated and 224 downregulated) in the high-dose
dietary genistein treated group in comparison with the control (P < 0.05, |log2FoldChange| > 0.585). Therefore, high-dose
dietary genistein altered the hypothalamic RNA profile and signal
processing. Cluster analysis further revealed that high-dose dietary
genistein significantly influenced apoptosis, the immune process,
and the whole synthesis of steroid hormones in the hypothalamus (P < 0.05). In conclusion, high-dose dietary genistein
altered the hypothalamic RNA profile and intestinal health of female
chicks.

染料木黄酮（Genistein）广泛存在于动物饲料中。本研究评估了高剂量染料木黄酮对肠道健康以及下丘脑RNA表达谱的影响。
通过腹腔注射（剂量参数为416 ± 21，34.5 ± 2.5）与饲料添加（剂量参数为308 ± 19，27.2 ± 2.1）方式暴露于高剂量染料木黄酮的雏鸡，与对照组（261 ± 16，22.7 ± 1.6，P < 0.01）相比，均出现体重增重与采食量下降的情况。
与对照组（22.4 ± 0.5，33.3 ± 2.4）相比，高剂量染料木黄酮注射组（21.6 ± 0.5，31.8 ± 1.6）与饲料添加组（20.6 ± 0.9，29.9 ± 2.5，P < 0.001）的血清白蛋白与总蛋白水平均显著降低。
有趣的是，饲喂染料木黄酮的雏鸡下丘脑中苦味受体TAS1R3的表达出现下调（P < 0.05）。
与此同时，该处理还上调了回肠中TAS2R1（P < 0.05）及其下游基因PLCB2与IP3R3的表达（P < 0.05）。
相应地，高剂量饲料添加染料木黄酮会降低回肠绒毛高度以及乳酸杆菌（Lactobacillus）的丰度，同时增加回肠中致病细菌的丰度（P < 0.05）。
此外，转录组学分析显示，与对照组相比，高剂量饲料添加染料木黄酮处理组中共鉴定出348个差异表达基因（其中168个上调、224个下调），差异具有统计学意义（P < 0.05，|log₂折叠变化| > 0.585）。
因此，高剂量饲料添加染料木黄酮会改变下丘脑的RNA表达谱与信号加工过程。
聚类分析进一步显示，高剂量饲料添加染料木黄酮可显著影响雏鸡下丘脑中的细胞凋亡、免疫过程以及类固醇激素的整体合成通路（P < 0.05）。
综上，高剂量饲料添加染料木黄酮会改变雌性雏鸡的下丘脑RNA表达谱与肠道健康状态。