Microbiomes and Inflammation in Chronic Fatigue Syndrome

慢性疲劳综合征中的微生物组和炎症

• 批准号: 8359145
• 负责人: MAUREEN REBECCA HANSON
• 金额: $ 22.72万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359145
• 关键词: Affect; Arthralgia; Bacteria; Bacterial Translocation; Bacterial Typing; Biological Assay; Blood; Blood specimen; Cells; Chronic; Chronic Fatigue Syndrome; Chronically Ill; Communication; Communities; Consult; Cytokine Network Pathway; Databases; Diagnosis; Disease; Disease Outbreaks; Endotoxins; Epithelial Cells; Etiology; Exercise; Exhibits; Fatigue; Feces; Functional disorder; Gene Expression; Gene Expression Profile; Genes; Gut associated lymphoid tissue; Headache; Health; Human; Human Microbiome; Immune; Immune response; Immune system; Individual; Inflammation; Inflammatory; Inflammatory disease of the intestine; Intestinal Mucosa; Intestines; Knowledge; Lactoferrin; Lipopolysaccharides; Literature; Measures; Memory; Methods; Microbe; Mucosal Immunity; Myalgia; Natural Killer Cells; Patients; Pattern; Pharmaceutical Preparations; Physical Function; Probiotics; Psyche structure; RNA; Recombinant DNA; Sampling; Signaling Molecule; Sleep; Sore Throat; Symptoms; Taxon; antimicrobial; chemokine; chemokine receptor; cytokine; cytotoxicity; gastrointestinal symptom; immune activation; immune function; inflammatory marker; insight; lymph nodes; microbial; microbiome; peripheral blood; rRNA Genes

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.

描述（由申请人提供）：慢性疲劳综合症（CFS）是一种使人衰弱的疾病，其特征是长期疲劳和其他症状，例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、新发头痛、睡眠不佳和运动不耐受。慢性疲劳综合症患者经常表现出胃肠道症状。虽然慢性疲劳综合症的病因尚未确定，但许多疾病的爆发都与传染性病因有关。 CFS 患者的免疫系统表现出慢性激活和功能障碍。炎症细胞因子水平升高可能会引起许多疾病症状。众所周知，肠道免疫细胞和肠道微生物之间会发生串扰。由于免疫系统功能失调而导致的肠道微生物群落改变可能是某些慢性疲劳综合症症状的原因，并通过影响粘膜免疫和破坏肠道完整性，从而导致细菌从肠道易位到血液中，从而导致慢性免疫激活。我们将确定慢性疲劳综合症患者和健康个体血液和肠道中发现的细菌类型是否不同。将通过焦磷酸测序和 16S rDNA 序列分析，确定 48 名慢性病患者的血液和肠道微生物组的细菌组成，并与 24 名健康对照者进行比较。将进行检测以评估从肠道脱落的人体细胞中与免疫系统相关的基因的表达水平。粪便样本中乳铁蛋白的含量将被确定为炎症的衡量标准，细菌内毒素的含量将被确定为肠道功能障碍的指标。典型相关分析将用于识别患者亚群与健康个体中相关的细菌分类群和基因表达模式。此类探索性研究可能会提出将肠道微生物组转向更健康个体的治疗方法，以期改善症状，并可能揭示是否有必要进行益生菌和抗菌药物或特定炎症调节药物的试验。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宝贵贡献。 公共卫生相关性：慢性疲劳综合症 (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是否（1）肠道细胞中影响免疫反应的基因表达发生改变，以及（2）肠道中存在不同的微生物群，这可能是由于免疫系统与肠道微生物居民之间的通讯紊乱造成的。