Abstract：
Chronic constipation has been associated with depression-like behavior. Previous study identified the crucial role of gut microbiota in the development of constipation and depression. Dietary inulin (INU) could regulate gut microbiota. Whether INU treatment could ameliorate constipation induced depression was not clear. For this purpose, male CD-1 mice were administered diphenoxylate (20 mg/kg body weight/day) to induce constipation. We found that INU (10 % in standard diet) alleviated the diphenoxylate-induced constipation, manifested as the increase weight and moisture content of feces. Furthermore, the associated depression and anxiety-like behavior disorders were improved by inhibiting neuro-inflammation and preventing synaptic ultrastructure damage under INU treatment. Moreover, INU pretreatment improved the diphenoxylate-induced gut barrier damage by upregulating tight junction protein expression. INU also reshaped gut microbiota in constipation mice by increasing the relative abundance of Bacteroides and Proteobacteria and downregulating the abundance of Muribacalum and Melaminabacteria. The effects of INU on diphenoxylate-induced depression were abolished by gut microbiota depletion via antibiotic treatment. In addition, INU increased the concentration of short chain fatty acids (SCFAs) in feces contents. Meanwhile, supplementation of SCFAs could also partly improve diphenoxylate-induced depression. In conclusion, INU intake was a potential nutritional intervention strategy to prevent constipation induced depression via microbiota-gut-SCFAs axis.
摘要：
慢性便秘与抑郁样行为有关。先前的研究确定了肠道微生物群在便秘和抑郁症发展中的关键作用。膳食菊粉（INU）可以调节肠道菌群。INU治疗是否可以改善便秘引起的抑郁症尚不清楚。为此,向雄性CD-1小鼠施用苯乙氧基化物(20mg/kg体重/天)以诱导便秘。我们发现INU（标准饮食中的10％）可以缓解苯乙氧基化物引起的便秘，表现为粪便重量和水分含量的增加。此外，在INU治疗下,相关的抑郁和焦虑样行为障碍通过抑制神经炎症和预防突触超微结构损伤得到改善.此外，INU预处理通过上调紧密连接蛋白表达改善苯乙氧基化物诱导的肠屏障损伤。INU还通过增加拟杆菌和变形杆菌的相对丰度并下调Muribacalum和Melaminabacteria的丰度来重塑便秘小鼠的肠道微生物群。通过抗生素治疗，肠道微生物群的消耗消除了INU对苯乙氧基化物诱导的抑郁症的影响。此外,INU增加了粪便内容物中短链脂肪酸（SCFA）的浓度。同时,补充SCFA也可以部分改善苯乙氧基化物诱导的抑郁症。总之,INU摄入是通过微生物群-肠道-SCFAs轴预防便秘诱导的抑郁症的潜在营养干预策略。
