Microbiomes and Inflammation in Chronic Fatigue Syndrome

描述（由申请人提供）：慢性疲劳综合征（CFS）是一种衰弱性疾病，其特征是长期疲劳，并伴有其他症状，如记忆或注意力受损、喉咙痛、淋巴结痛、肌肉痛、多关节痛、新发头痛、睡眠不清和运动不耐受。慢性疲劳综合症患者通常表现为胃肠道症状。虽然慢性疲劳综合征的病因尚未确定，但一些疾病的爆发与感染性病因有关。慢性疲劳综合症患者表现出免疫系统的慢性激活和功能障碍。炎症细胞因子水平的升高可能导致这种疾病的许多症状。众所周知，肠道免疫细胞和肠道内的微生物之间会发生串扰。由于免疫系统功能失调，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导致慢性免疫激活，从而允许细菌从肠道转运到血液中。我们将确定血液和肠道中发现的细菌类型在慢性疲劳综合症患者和健康个体之间是否存在差异。将通过焦磷酸测序和16S rDNA序列分析，确定48名慢性患者的血液和肠道微生物组的细菌组成，并与24名健康对照进行比较。将进行检测，以评估从肠道脱落的人类细胞中与免疫系统相关的基因表达水平。粪便样本中乳铁蛋白的数量将被确定为炎症和细菌内毒素的衡量指标，作为肠道功能障碍的指示。典型相关分析将用于确定患者亚群与健康个体之间相关的细菌分类群和基因表达模式。这样的探索性研究可能会提出将肠道微生物群转向更健康个体的治疗方法，以期改善症状，并可能揭示益生菌和抗菌药物或特定炎症调节药物的试验是否有必要。由于人类微生物群的表征才刚刚开始，我们的分析也将为了解与CFS相关的微生物多样性做出有价值的贡献。

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.