Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity, by Amy D Proal and Trevor Marshall in Front. Pediatr. 4 Dec 2018
The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities.
Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body towards a state of illness.
Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens.
Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient’s unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.
Excerpt from Discussion:
…It often takes patients years to receive a diagnosis of ME/CFS. This delay wastes a valuable period during which the immune system is most responsive to immunostimulatory treatment. Patients treated during earlier stage disease are also less likely to experience severe or long-lasting immunopathology. This suggests that immunostimulative therapies should be administered in a predictive and even preventative fashion. In addition, interventions or treatments that might help patients better manage the byproducts of immunopathology (bacterial LPS etc.) should become a priority for the research community.
The overall success of ME/CFS research also hinges on the scientific community’s willingness to embrace the concept of the human holobiont. In ME/CFS, the immune response, metabolism, central nervous system, and human gene expression are all linked by the activity of the microbiome and its associated proteins/metabolites. A greater focus on these interconnected systems is necessary, which will require increased collaboration between separate research teams.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease characterized by unexplained incapacitating fatigue, accompanied by variable multi-systemic symptoms. ME/CFS causes a significant personal and public health burden, and urgently requires the coordination of research efforts to investigate its etiology and
To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics.
A long time advocate and sufferer of ME, Dr Anne McIntyre, died on Saturday 24th November 2018. She had been living with rheumatoid arthritis for many years and developed pulmonary fibrosis as a complication of that.
Some studies have employed tilt table tests lasting 2-5 minutes to diagnose one common form of orthostatic intolerance, postural tachycardia syndrome (POTS). We examined the diagnostic yield of abbreviated durations of tilt testing in adults meeting criteria for ME/CFS, and identified the proportion with POTS misdiagnosed using testing of less than 10 minutes.
Conflicting data have been published on the reduction of circulating blood volume in adults with Myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). The aim of the present study was to compare blood volumes based on the presence or absence of 
One of the key requirements of a reliable case definition is the use of standardized procedures for assessing symptoms. This article chronicles the development of the DePaul Symptom Questionnaire (DSQ) to assess symptoms of the major chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) case definitions.
