Effects of gut microbiota remodeling on the dysbiosis induced by high fat diet in a mouse model of Gulf war illness.
Effects of gut microbiota remodeling on the dysbiosis induced by high fat diet in a mouse model of Gulf war illness.
复制标题
肠道菌群重塑对海湾战争病小鼠高脂饮食诱导的生态失调的影响
DOI：
10.1016/j.lfs.2021.119675
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发表时间：
2021-08-15
期刊：
影响因子：
6.1
通讯作者：
Kuhn DM
中科院分区：
文献类型：
--
作者：
Angoa-Pérez M;Zagorac B;Francescutti DM;Theis KR;Kuhn DM
海湾战争病(GWI)是一种病因不明的慢性疾病，以疼痛、疲劳、胃肠功能障碍和神经认知问题等多种症状为特征。越来越多的证据表明，肠道微生物群的扰动在这种疾病的病理中发挥了关键作用。GWI的病程是肠道微生物区系改变及其代谢物(例如，短链脂肪酸-SCFA-)，生活方式风险因素，如高脂肪饮食(HF)，可加重这种改变。为了探讨肠道微生物群的致病作用，我们用不可吸收抗生素(ABX)对GWI制剂治疗的小鼠进行治疗，并同时喂饲HF。鉴于ABX作为假无菌动物模型的广泛应用，我们评估了ABX暴露于GWI和HF对体重、食物摄入量、肠道微生物区系变化和SCFA醋酸酯水平的影响。结果表明，在对照组和GWI中，HF减少了食物的摄入量，同时增加了体重。暴露于ABX可通过抵消GWI中的体重增加来预防这些HF效应。GWI和HF导致α多样性降低，肠道细菌群落的组成和结构遭到破坏，醋酸盐水平下降。这种由ABX诱导的肠道微生物群重塑的特征是变形杆菌的扩张，类杆菌和细菌的减少，以及醋酸盐水平的总体上升，以及潜在病原体的增殖。因此，使用ABX可能不代表一种可靠的耗尽肠道微生物组的方法，它作为一种伪无菌模型的优势值得进一步研究。
Gulf war illness (GWI) is a chronic disorder of unknown etiology characterized by multiple symptoms such as pain, fatigue, gastrointestinal disturbances and neurocognitive problems. Increasing evidence suggests that gut microbiome perturbations play a key role in the pathology of this disorder. GWI courses with gut microbiota alterations and their metabolites (e.g. short chain fatty acids -SCFA-), which can be aggravated by lifestyle risk factors such as a high fat diet (HF). To investigate the causative role of the gut microbiome, non-absorbable antibiotics (Abx) were administered to mice treated with GWI agents and concomitantly fed with a HF. In light of the wide use of Abx as pseudo-germ-free models, we evaluated the effects of Abx exposure on GWI and HF on body weight, food intake, gut microbiota changes and levels of the SCFA acetate. Results show that HF decreased food intake while increasing body weight in both controls and GWI. Exposure to Abx prevented these HF effects by offsetting the body weight gain in GWI. GWI and HF led to decreases in α-diversity, disruptions in the composition and structure of the gut bacterial community and decreases in acetate levels. This Abx-induced remodeling of the gut microbiome was characterized by an expansion of Proteobacteria, decreases in Bacteroidetes and Firmicutes, and overall increases in acetate levels, as well as by the proliferation of potential pathobionts. Therefore, the use of Abx may not represent a dependable approach to deplete the gut microbiome and its advantages as a pseudo germ-free model warrant further investigation.