Microbiomes and Inflammation in Chronic Fatigue Syndrome

描述(申请人提供)：慢性疲劳综合症(CFS)是一种以长期疲劳和其他症状为特征的衰弱疾病，如记忆力或注意力受损、喉咙痛、淋巴结压痛、肌肉疼痛、多关节疼痛、新出现的头痛、睡眠不清新和运动耐受。慢性疲劳综合征患者通常会出现胃肠道症状。虽然慢性疲劳综合征的病因(S)尚未确定，但一些疫情的爆发涉及感染性病因学。CFS患者表现出免疫系统的慢性激活和功能障碍。炎性细胞因子水平的增加可能会导致疾病的许多症状。已知的串扰发生在肠道免疫细胞和肠道中的微生物之间。由于免疫系统功能失调而引起的肠道微生物群落的改变可能导致一些CFS症状，并通过影响粘膜免疫和破坏肠道完整性而导致慢性免疫激活，从而允许细菌从肠道移位到血液中。我们将确定在CFS患者和健康人之间，血液和肠道中发现的细菌类型是否不同。通过焦磷酸测序和16S rDNA序列分析，将测定48名慢性病患者血液和肠道微生物群的细菌组成，并与24名健康对照组进行比较。将进行检测，以评估与免疫系统相关的基因在从肠道脱落的人类细胞中的表达水平。粪便样本中乳铁蛋白的含量将作为炎症的衡量标准，细菌内毒素的含量将作为肠道功能障碍的指标。典型相关分析将被用来识别相关的细菌分类群和患者亚群与健康个体之间的基因表达模式。这样的探索性研究可能会建议一些治疗方法，将肠道微生物群转移到更健康的个人身上，希望能改善症状，并可能揭示是否有必要试验益生菌和抗菌剂或特定的抗炎药物。由于人类微生物区系的表征才刚刚开始，我们的分析也将对了解与CFS相关的微生物多样性做出有价值的贡献。 公共卫生相关性：慢性疲劳综合征(CFS)是一种损害精神和身体功能的致残性疾病，通常与胃肠道症状有关。我们将确定这些患者(1)是否有影响免疫反应的基因表达改变的肠道细胞，以及(2)他们的肠道中是否有不同的微生物群，这可能是由于免疫系统和肠道微生物之间的通信障碍造成的。

DESCRIPTION (provided by applicant): Chronic fatigue syndrome (CFS) is a debilitating illness characterized by long-term fatigue and by other symptoms such as impaired memory or concentration, sore throat, tender lymph nodes, muscle pain, multi-joint pain, new headaches, unrefreshing sleep, and exercise intolerance. Individuals with CFS often exhibit gastrointestinal symptoms. While the cause(s) of chronic fatigue syndrome has not been established, a number of outbreaks implicate an infectious etiology. CFS patients exhibit both chronic activation and dysfunction of their immune systems. Increased levels of inflammatory cytokines could engender many of the symptoms of the illness. Cross-talk is known to occur between the intestinal immune cells and the microbes that reside in the gut. An altered community of gut microbes due to a dysfunctional immune system could be responsible for some CFS symptoms and contribute to chronic immune activation by affecting mucosal immunity and by disrupting intestinal integrity, thus allowing translocation of bacteria into blood from the gut. We will determine whether the types of bacteria found in the blood and gut differ between CFS patients and healthy individuals. The bacterial composition of the blood and gut microbiomes will be determined in 48 chronically ill individuals and compared to 24 healthy controls by pyrosequencing and analysis of 16S rDNA sequences. Assays will be performed to assess the expression levels of genes relevant to the immune system in human cells shed from the intestine. The amount of lactoferrin in stool samples will be determined as a measure of inflammation and bacterial endotoxin as an indication of intestinal dysfunction. Canonical correlation analysis will be used to identify correlated bacterial taxa and patterns of gene expression within patient subsets vs. healthy individuals. Such exploratory studies might suggest therapies to shift the gut microbiome toward that of healthier individuals in the hopes of ameliorating symptoms and could reveal whether trials of probiotics and antimicrobial or particular inflammation-modulating drugs may be warranted. Because characterization of the human microbiota is just beginning, our analyses will also make a valuable contribution to knowledge about the diversity of microbes associated with CFS. PUBLIC HEALTH RELEVANCE: Chronic fatigue syndrome (CFS) is a disabling illness that impairs mental and physical function and is often associated with gastrointestinal symptoms. We will determine whether such patients (1) have intestinal cells with altered expression of genes that affect immune responses and (2) have a different constellation of microbes in their gut, possibly resulting from disturbances in communication between the immune system and the microbial inhabitants of the intestine.