糖尿病并发抑郁症大鼠肠道菌群失衡初步研究

目的 通过对糖尿病并发抑郁症(diabetes-related depression, DD)大鼠肠道微生物进行16s rRNA测序分析，探讨该疾病状态下肠道菌群的改变。方法 建立DD模型，以健康SD大鼠作为空白对照组。每周称量体重的同时进行空腹血糖检测；采用强迫游泳和矿场实验检测大鼠行为学；对各组大鼠肠道内容物进行16s rRNA测序；以血清为检测对象，对下丘脑-垂体-肾上腺轴(hypothalamic-pituitary-adrenal axis, HPA轴)相关蛋白及细菌脂多糖(lipopolysaccharide, LPS)含量进行检测。结果 与空白组比较，DD模型组血糖显著升高并表现出明显抑郁样行为和HPA轴亢进；16s rRNA测序结果提示，与空白组比较，DD模型组肠道菌群α多样性(Chao、Simpson、Shannon指数)无明显差异；但β多样性差异明显，即空白组与DD模型组的样品间距离较远；肠道菌群组间差异明显，与空白组比较，DD模型组中厚壁菌门丰度明显降低(P<0.01),而拟杆菌门则无明显差异；Bugbase表型预测提示，与空白组比较，DD模型组中革兰氏阴性...

Preliminary study on the imbalance of gut microbiota in rats with diabetes mellitus complicated by depression

Objective To explore the alteration of gut microbiota in the disease state by 16s rRNA sequencing analysis of intestinal microbial population in rats with diabetes-related depression (DD). Methods A DD model was established, and healthy SD rats were used as the blank control group. The rats were weighed weekly, and fasting blood glucose was measured simultaneously. After the model was established, the rats’ behavior was examined by forced swimming test and open field test. The intestinal contents of rats in each group were collected, and 16s rRNA sequencing was performed and analyzed. The serum contents of hypothalamic-pituitary-adrenal (HPA) axis-related proteins and lipopolysaccharide (LPS) in rats of each group were detected. Results Compared with the blank control group, the DD model group showed significantly higher blood glucose and exhibited significant depression-like behavior and HPA axis hyperactivity. 16s rRNA sequencing results displayed that compared with the blank control group, α diversities (Chao, Simpson and Shannon indexes) of gut microbiota in the DD model group were not significantly different, but β diversity was significantly different, and the distance between samples in the blank control group and the DD model group was far. The gut microbiota differed significantly between groups. The abundance of phylumFirmicutes in the DD model group was significantly lower compared with the blank control group (P<0.01), while phylumBacteroidetes was not significantly different. Bugbase phenotypic prediction analysis showed significantly higher gram-negative bacteria and higher serum level of LPS in the DD model group compared with the blank control group. Conclusion The gut microbiota in the DD model group is disorderly distributed, with changes different from those in diabetes or depression alone. Gut microbiota disturbance leads to an increase in conditionally pathogenic bacteria in DD and thus results in a rise in LPS, which may be related to HPA axis hyperactivity.