Microbiomes and Inflammation in Chronic Fatigue Syndrome

描述（由申请人提供）：慢性疲劳综合征（CFS）是一种使人衰弱的疾病，其特征是长期疲劳和其他症状，如记忆力或注意力受损、咽喉痛、淋巴结触痛、肌肉疼痛、多关节疼痛、新发头痛、睡眠不振和运动不耐受。CFS患者经常表现出胃肠道症状。虽然慢性疲劳综合征的病因尚未确定，但一些暴发涉及感染性病因。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引起疾病的许多症状。众所周知，肠道免疫细胞和肠道中的微生物之间会发生串扰。由于免疫系统功能失调而改变的肠道微生物群落可能是导致某些CFS症状的原因，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，从而使细菌从肠道易位到血液中。我们将确定CFS患者和健康个体之间血液和肠道中发现的细菌类型是否不同。将在48名慢性病患者中确定血液和肠道微生物组的细菌组成，并通过焦磷酸测序和16S rDNA序列分析与24名健康对照进行比较。将进行测定以评估从肠脱落的人细胞中与免疫系统相关的基因的表达水平。粪便样品中乳铁蛋白的量将被确定为炎症和细菌内毒素的量度，作为肠功能障碍的指示。典型相关分析将用于鉴定患者亚组与健康个体内相关的细菌分类群和基因表达模式。这些探索性研究可能会建议将肠道微生物组转移到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微生物或特定炎症调节药物的试验是否有必要。由于对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宝贵贡献。 公共卫生相关性：慢性疲劳综合征（CFS）是一种致残性疾病，损害精神和身体功能，往往与胃肠道症状。我们将确定这些患者是否（1）具有影响免疫反应的基因表达改变的肠细胞，以及（2）肠道中有不同的微生物群，可能是由于免疫系统和肠道微生物居民之间的沟通障碍造成的。

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.