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

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.

Probiotics: If It Does Not Help It Does Not Do Any Harm. Really?

“…The enteric prophages serve as a mobile repository of genetic elements and are transmitted via our microbiome, thus impacting on the microbiota/dysbiota or symbionts/pathbionts ratios and health and disease [101,102]. The enteric phageome virulence is controlled by the neighboring microbes, fungi, and helminths, thus creating a luminal trans-kingdom relationship [103,104].…”

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance

“…4B). We think this finding represents another clue into ME-pathogenesis and the mechanism of action of INMEST, since the gut microbes and dysbiosis is likely in ME (20), and the vagus nerve conveying such afferent signals from the gut to the brainstem and inducing immune regulation via the inflammatory reflex (27,28). The reduction in plasma IL-17A and CCL28 levels after INMEST and the restored MAIT/Regulatory T-cell relationship indicate a modulation of this axis by INMEST treatment and mitigation of an inflammatory state originating at the immune microbe interface in the intestine.…”

“…Direct infection of vagus nerve fibers has been suggested as a possible pathogenic mechanism in ME (18) and some patients with cervical compression involving the vagus nucleus present with ME-like symptoms, sometimes reversible upon decompressive surgery (19). Moreover, afferent fibers in the vagus nerve can sense microbial stimuli and dysbiosis in the gut and elsewhere that fuel the chronic inflammation in ME (20).…”

Multi-omics Examination of Q Fever Fatigue Syndrome Identifies Similarities with Chronic Fatigue Syndrome

“…Investigations of the metabolome (16)(17)(18)(19)(20) and (gut) microbiome (21)(22)(23)(24)(25) in CFS, both aspects that are inadvertently linked with in ammation (16,26), showed interesting, albeit inconsistent, results (23,25). Up until this moment, no such studies were conducted in QFS.…”