An interesting opinion review article was recently published in Frontiers in Pediatrics, and discusses ME/CFS research about the immune system, microbiome, metabolome, and other fields, and then uses this information to generate a hypothesis on ME/CFS symptoms. The authors also put forward some interesting hypotheses on potential new treatment approaches.
ME/CFS has been strongly linked to infectious agents, including Epstein Barr Virus (EBV), Lyme disease, Herpes Virus 6 (HHV6), and many others. But researchers have been unable to pinpoint a definite infectious agent. The primary author of the review, Amy Proal, argues that since many well-studied inflammatory conditions are now being tied to dysbiosis, or disruption, of the human microbiome, initial infection with various agents could be causing similar clusters of inflammatory symptoms seen in ME/CFS.
Proal thinks that ME/CFS may be caused by successive infection, which is when an original acute infection or immunosuppressive event dysregulates the immune system. Many pathogens have evolved survival mechanisms that allow them to disable the host immune response, and they can also control the human metabolism, as well as gene expression, through their secreted proteins and metabolites. These abilities can promote community-wide virulence in pathogenic members of the microbiome; bacteria who would normally benefit the human host, but who can become pathogenic when the immune system is weakened. This causes a snowball effect where the microbiome becomes increasingly dysbiotic as the immune system weakens over time, causing ME/CFS to develop. The large variation seen in ME/CFS symptoms is potentially caused by the patient’s unique infectious and environmental history, as well as by the virulence of the pathogens driving the dysbiosis.
Antibiotics and immunosuppressive drugs can compound the problem, as antibiotics can disrupt the ecology of the human microbiome, and immunosuppressive drugs can further weaken the immune system. Proal concludes: “If ME/CFS is driven by successive infection, treatments that support or activate the human immune system could improve microbiome health by allowing patients to better target persistent pathogens. Development of such therapies should be a priority for the ME/CFS research community.”