仔猪肠道菌群紊乱通过迷走神经末梢受体调控食欲的肠-脑轴机制

肠道菌群紊乱导致的采食量降低是限制断奶仔猪生长的重要因素，但其作用机制尚不清楚。申请人前期研究发现：将腹泻仔猪的粪菌移植给小鼠，可显著抑制小鼠采食，同时发现迷走神经末梢的白介素受体表达升高、中枢孤束核神经元兴奋；而切断小鼠迷走传入神经后，则对其采食无影响。由此推测：仔猪肠道迷走神经末梢上的白介素受体可能通过感应肠道菌群紊乱信号，经孤束核投射引起食欲降低。为验证该假设，本项目首先选择不同腹泻程度和不同采食量的断奶仔猪，对粪便炎症因子水平、肠道微生物区系和采食量进行关联分析；随后，研究腹泻仔猪粪菌移植对迷走传入神经切除前后健康受体猪的采食量、结状神经节和孤束核兴奋性的影响，以及肠道迷走神经末梢白介素受体表达的影响；最后，运用光遗传学和神经元特异性敲除等技术，研究迷走传入神经及其白介素受体介导肠道菌群紊乱调控仔猪采食的机制。研究结果对深入揭示肠道菌群紊乱导致食欲降低的肠-脑轴机制具有重要意义。

Intestinal flora imbalance induced food intake reduction is an important factor limiting the growth of weaned piglets, but its mechanism is still unclear. The applicant’s preliminary research found that transplanting fecal microbiota from diarrhea piglets to mice can significantly inhibit the mice food intake, increase the expression of interleukin receptors in vagal afferent nerves terminal and activate the nucleus tractus solitarius neurons. However, fecal microbiota transplantation had no effect on food intake after subdiaphragmatic vagotomy. It is speculated that the interleukin receptors on the terminal of intestinal vagal afferent nerve may reduce appetite of piglets by sensing the signal of intestinal flora imbalance and projecting to the nucleus tractus solitaries. To test this hypothesis, the correlation of fecal inflammatory factors, gut microbiota and food intake of weaned piglets with different diarrhea degree and different food intake are analyzed. Subsequently, the effects of transplanting fecal bacteria from diarrhea to healthy recipient piglets on the food intake, excitability of nodose ganglion or nucleus tractus solitarius neurons and expression of interleukin receptors in the vagal nerve terminals of the intestinal before and after subdiaphragmatic vagotomy were studied. Finally, optogenetics and neuron specific knockout techniques were used to research the mechanism of vagal afferent nerve and its interleukin receptor mediated intestinal flora imbalance regulating piglet food intake. The results have a great significance to further reveal the gut-brain axis mechanism of intestinal flora imbalance induced anorexia.