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Review
. 2018 Dec 4;6:373.
doi: 10.3389/fped.2018.00373. eCollection 2018.

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

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Free PMC article
Review

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

Amy Proal et al. Front Pediatr. .
Free PMC article

Abstract

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 toward 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.

Keywords: ME/CFS; autoantibody; dysbiosis; gut-brain axis; holobiont; microbiome; molecular mimicry; pathobiont.

Figures

Figure 1
Figure 1
The IMG/VR database catalogs viruses in Earth's ecosystems including the human body. Viral diversity in IMG/VR has more than tripled since August 2016.
Figure 2
Figure 2
Venn diagram of the qualitative distribution of proteins identified in cerebrospinal fluid from normal control subjects and ME/CFS subjects. Seven hundred and thirty eight of 2,783 identified proteins (26.5%) were unique to patients with ME/CFS. The numbers of proteins for each category separately is shown outside the circles (2,630 for normal controls, 2,783 for ME/CFS) (94).
Figure 3
Figure 3
Intracellular pathogens and the proteins/metabolites they express can directly interfere with human transcription, translation, and DNA repair processes.
Figure 4
Figure 4
VDR activity is downregulated as much as 20 times in Epstein Barr Virus-infected lymphoblastoid cell lines (128).

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