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Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation
Brain, Behavior, and Immunity ( IF 15.1 ) Pub Date : 2022-03-05 , DOI: 10.1016/j.bbi.2022.03.001
Fernando A Vicentini 1 , Jake C Szamosi 2 , Laura Rossi 2 , Lateece Griffin 3 , Kristoff Nieves 4 , Dominique Bihan 5 , Ian A Lewis 5 , Quentin J Pittman 6 , Mark G Swain 7 , Michael G Surette 2 , Simon A Hirota 8 , Keith A Sharkey 9
Affiliation  

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.



中文翻译:

在没有炎症的情况下,结肠炎相关微生物群驱动雄性小鼠的行为变化

炎症性肠病 (IBD) 是胃肠道的慢性炎症性疾病。IBD 与认知、行为和情绪合并症的高发相关,包括焦虑和抑郁。IBD 与行为合并症的发展之间的联系知之甚少。由于肠道微生物群深刻影响宿主行为,我们试图确定与肠道炎症相关的肠道微生物群改变是否有助于行为异常的发展。使用结肠炎的葡聚糖硫酸钠 (DSS) 模型,我们对雄性小鼠的肠道炎症、行为(升高的迷宫和悬尾试验)和微生物群的组成进行了表征。将结肠炎小鼠的盲肠内容物转移到无菌 (GF) 或抗生素 (Abx) 处理的小鼠中,并在受体小鼠中表征行为。使用qPCR测量基因表达。DSS 结肠炎的特征是体重显着降低和结肠炎症标志物增加。这些变化伴随着焦虑样行为的增加、肠道微生物群组成的改变以及中枢神经系统的增加。肿瘤坏死因子表达。来自结肠炎小鼠的盲肠物质的转移在 GF 和 Abx 治疗的受体小鼠中引起了类似的行为变化,没有结肠或神经炎症的迹象。在对供体和受体小鼠的微生物群进行表征后,发现特定的分类群与行为变化有关,特别是毛螺菌科的成员。与肠道炎症相关的行为异常可通过盲肠物质的转移传播,这表明肠道微生物群组成的改变在驱动结肠炎的行为变化中起关键作用。

更新日期:2022-03-05
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