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.

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